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{{Taxobox
| color = lightgreen
| name = St John's wort
| image = Saint johns wart flowers.jpg
| image_width = 250px
| regnum = [[Plant]]ae
| divisio = [[Flowering plant|Magnoliophyta]]
| classis = [[Dicotyledon|Magnoliopsida]]
| ordo = [[Malpighiales]]
| familia = [[Clusiaceae]]
| genus = ''[[Hypericum]]''
| species = '''''H. perforatum'''''
| binomial = ''Hypericum perforatum''
| binomial_authority = [[Carolus Linnaeus|L.]]
}}
'''St John's wort''' ([[International Phonetic Alphabet|IPA pronunciation]]: [[General American]] {{IPA|[-wɝt]}}, [[Received Pronunciation]] {{IPA|[wɜːt]}}, rhyming with ''fort'') used alone refers to the species ''Hypericum perforatum'', also known as '''Tipton's Weed''' or '''Klamath weed''', but, with qualifiers, is used to refer to any species of the genus ''[[Hypericum]]''. Therefore, ''H. perforatum'' is sometimes called '''Common St John's wort''' to differentiate it. The species of ''Hypericum'' have been placed by some in the family [[Hypericaceae]], but more recently have been included in the [[Clusiaceae]].{{Fact|date=February 2007}} Approximately 370 species of the genus ''Hypericum'' exist worldwide with a native geographical distribution including temperate and subtropical regions of North America, Europe, Asia Minor, Russia, India and China.
==The plant==
''Hypericum perforatum'' is a yellow-flowering, [[rhizome|rhizomatous]], [[perennial plant|perennial]] [[herb]] indigenous to Europe, which has been introduced to the Americas and grows wild in many meadows. The common name comes from its traditional flowering and harvesting on [[John the Baptist|St John's]] day, [[24 June]]. The [[genus]] name ''Hypericum'' is derived from the Greek words ''hyper'' (above) and ''eikon'' (picture), in reference to the traditional use of the plant to ward off evil, by hanging plants over a picture in the house during St John's day. The [[species]] name ''perforatum'' refers to the presence of small oil glands in the leaves that look like windows, which can be seen when they are held against the light.
Although ''Hypericum perforatum'' is grown commercially in some regions of south east Europe, it is listed as a noxious weed in more than twenty countries. In pastures, St John’s wort acts as both a toxic and invasive weed.<ref>http://www.northwestweeds.nsw.gov.au/st_johns_wort.htm</ref> It replaces useful vegetation to the extent of making productive land unviable or acts as an alien species in natural ecosystems. Ingestion by livestock can cause photosensitization, central nervous system depression, spontaneous abortion, and can lead to death. Effective herbicides for control of ''Hypericum'' include [[2,4-D]], picloram, and [[glyphosate]]. In western [[North America]] three beetles ''[[Chrysolina quadrigemina]]'', ''[[Chrysolina hyperici]]'' and ''[[Agrilus hyperici]]'' have been introduced as [[biocontrol]] agents.
==Identification==
St John’s wort can be visually recognized by leaf and flower type. Yellow, five petaled flowers approximately 20 mm across occur between late Spring and early to mid Summer. Leaves exhibit obvious translucent dots when held up to the light, giving them a ‘perforated’ appearance, hence the plant's Latin name. When flowers or seed pods are crushed, a reddish/purple liquid is produced.
[[Image:StJohnswortID.jpg|right|thumb|''The translucent dots on the St John's wort leaves'']]
==Botanical description==
St John's wort is a [[perennial plant]] with extensive, creeping [[rhizomes]]. <!-- barren shoots prostrate | QUESTION: not sure what this means or how to turn it into a sentence--> Its stems are erect, branched in the upper section, and can grow to 1 m high. It has opposing, stalkless, narrow, oblong leaves which are 12 mm long or slightly larger. The leaves are yellow-green in color, with transparent dots throughout the tissue and occasionally with a few black dots on the lower surface. Its flowers measure up to 2.5 cm across, have five petals, and are colored bright yellow with conspicuous black dots. The flowers appear in broad [[inflorescence|cymes]] at the ends of the upper branches. The [[sepals]] are pointed, with glandular dots in the tissue. There are many [[stamens]], which are united at the base into three bundles.
==Ecology==
St John’s wort has a complex life cycle that includes a mature plant cycle with vegetative and sexual reproduction. It thrives in areas with either a winter- or summer-dominant rainfall pattern; however, distribution is restricted by temperatures too low for seed germination or seedling survival. Altitudes greater than 1500 m, rainfall less than 500 mm, and a daily mean January temperature greater than 24 degrees are considered limiting thresholds. Depending on environmental and climatic conditions, and rosette age, St John’s wort will alter growth form and habit to promote survival. Summer rains are particularly effective in allowing the plant to grow vegetatively, following defoliation by insects or grazing.
== Hypericum poisoning (livestock) ==
===Clinical signs===
At large doses, St John's wort is [[poison]]ous to grazing [[livestock]] (cattle, sheep, goats, horses).<ref>http://www.northwestweeds.nsw.gov.au/st_johns_wort.htm</ref> Behavioural signs of poisoning are general restlessness and skin irritation. Restlessness is often indicated by pawing of the ground, head shaking, 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 graziers include the appearance of circular patches giving hillsides a ‘crop circle’ appearance, possibly from this phenomenon. Animals typically seek shade and have reduced appetite. 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 [[Abortion|abort]]. Lesions on [[udder]]s are often apparent. Horses may show signs of [[Anorexia (symptom)|anorexia]], [[Depression (mood)|depression]] (with a comatose state), dilated pupils, and injected [[conjunctiva]].
===Early 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 more affected than old animals. In severe cases death may occur, as a direct result of starvation, or because of secondary disease or [[Sepsis|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 the milk production, or the transmission of a toxin in the milk.
===Photosensitisation===
Most clinical signs are caused by [[Photosensitivity|photosensitisation]].<ref>http://www.northwestweeds.nsw.gov.au/st_johns_wort.htm#effect_on_animals</ref> Plants may induce either primary or secondary photosensitisation: primary photosensitisation directly from chemicals contained in ingested plants, or 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 Hypericum-related effect on the excretory capacity of the liver, or any interference was minimal and temporary. However, at high and continuous dose rates changes in blood plasma indicative of some liver damage have been observed.
Photosensitisation causes skin inflammation by a mechanism involving a pigment or photodynamic compound, which when activated by a certain wavelength of light leads to [[Redox|oxidation]] reactions [[in vivo]]. This leads to lesions of tissue, particularly noticeable on and around parts of skin exposed to light. Lightly covered or poorly [[Biological pigment|pigment]]ed areas are most conspicuous. Removal of affected animals from sunlight results in reduced symptoms of poisoning.
==Use as Antidepressant==
In modern medicine, standardized ''Hypericum'' extract (obtained from ''H. perforatum'') is commonly used as a treatment for [[Clinical depression|depression]] and [[anxiety disorder]]s. In [[homeopathy]], ''Hypericum'' is used in the treatment of numerous medical problems, yet the rate of success has not been adequately documented.
St John's wort is today most widely known as a herbal treatment for [[Clinical depression|depression]]. In some countries, such as [[Germany]], it is commonly prescribed for mild depression, especially in children, adolescents, and where cost is a concern.<ref>Fegert J, Kölch M, Zito J, Gaeske G, Janhsen K (2006). [http://www.liebertonline.com/doi/abs/10.1089/cap.2006.16.197 Antidepressant Use in Children and Adolescents in Germany]. Journal of Child and Adolescent Psychopharmacology 16, 197-206.</ref> Standardized extracts are generally available [[Over-the-counter drug|over the counter]] – however, in some countries (such as [[Ireland]]) a prescription is required. Extracts are usually in [[tablet]] or [[encapsulation (pharmacology)|capsule]] form, and also in teabags and [[tincture]]s.
===Clinical evidence===
[[Image:Hypericum perforatum plantlets.jpg|thumb|250px|Seedlings of St John's wort]]
Clinical studies of St John's wort preparations have mainly focused on the efficacy of the herb in [[clinical depression]]. Several studies and [[meta-study|meta-analyses]] have found it to be effective in the treatment of mild to moderate depression, with fewer side effects than many conventional [[antidepressant]]s. Other studies, including a major NIH study that focused on moderate to severe depression, have shown no improvements.<ref>Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. Journal of the American Medical Association. 2002;287(14):1807–1814.</ref>
====Evidence for efficacy====
An early [[meta-study]] indicated that extracts of ''Hypericum'' may be more efficacious than placebo for the treatment of mild to moderately severe depressive disorders.<ref>Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D (1996). [http://bmj.bmjjournals.com/cgi/content/full/313/7052/253?view=full&pmid=8704532 St John’s wort for depression – an overview and meta-analysis of randomised clinical trials.] ''Br Med J'' '''313''', 253–258.</ref> This study, which covered the results from 23 smaller, earlier studies, is perhaps the most often cited by manufacturers and other supporters of St John's wort.
This study was later updated to include further studies, for a total of 27, to form a [[Cochrane Library|Cochrane Review]]. The updated review found that ''Hypericum'' preparations were significantly superior to placebo ([[rate ratio]] 2.47; 95% [[confidence interval]] 1.69 to 3.61) and similarly effective as standard antidepressants (single preparations 1.01; 0.87 to 1.16, combinations 1.52; 0.78 to 2.94).<ref name="linde_mulrow_2003">Linde K, Mulrow CD (2003). St John's wort for depression (Cochrane Review). In: ''The Cochrane Library'', Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.</ref>
Another meta-analysis, with stricter inclusion criteria, found that ''Hypericum'' was more efficacious than placebo; and as efficacious as [[tricyclic antidepressant]]s, with fewer adverse drug reactions.<ref>Kim HL, Streltzer J, Goebert D (1999). St. John's wort for Depression: A Meta-Analysis of Well-Defined Clinical Trials. ''J Ment Nerv Dis'' '''187''' (9), 532-538.</ref> This meta-analysis showed that the [[response rate]] for St John’s wort was significantly greater than that for placebo (73.2 versus 37.9%, respectively, [[relative risk]] 1.48 and 95% [[Confidence interval|CI]] 1.03–1.92) and similar to that observed with tricyclic antidepressants (64 versus 66.4% for St John’s wort and tricyclic antidepressants, respectively, relative risk 1.11 and 95% CI 0.92–1.29).
Other, more recent trials have also shown greater efficacy than placebo, and comparable efficacy to standard antidepressants with a superior adverse effect profile<!-- In English, please. -->.<ref name="woelk_et_al_2006">Woelk H, ''et al.'' (2000). Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. ''Br Med J'' '''321''', 536-9.</ref><ref name="schrader_et_al_2000">Schrader E, ''et al.'' (2000). Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomised, controlled study in mild-moderate depression. ''Int Clin Psychopharmacology'' '''15''', 61-68.</ref><ref>Laakmann G, Schule C, Baghai T, Kieser M (1998). St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. ''Pharmacopsychiatry'' '''31''' (Suppl 1), 54-9.</ref><ref>Harrer G, Schmidt U, Kuhn U, Biller A (1999). Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine. ''Arzneimittelforschung'' '''49''' (4), 289-96.</ref><ref>Philipp M, Kohnen R, Hiller KO (1999). Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. ''Br Med J'' '''319''' (7224), 1534-8.</ref><ref>{{cite journal | author=Szegedi A, Kohnen R, Dienel A, Kieser M | title=Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine | journal=BMJ | year=2005 | volume=330 | issue=7490 | pages=503–506 | url=http://bmj.bmjjournals.com/cgi/content/abstract/330/7490/503 }}</ref><ref>Lecrubier ''et al.'' "Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial." ''Am J Psychiatry''. 2002 Aug;159(8):1361-6. PMID 12153829 </ref>
Additionally, a 2006 study involving 150 patients with minor depressive symptoms or [[dysthymia]] found that St John's wort has a clinically significant effect in patients with minor depression, but not those suffering from dysthymia. It was concluded that St John's wort can be effective in the treatment of people with minor depression with a [[Hamilton Depression Rating Scale|Hamilton Depression Scale]] for Depression (HAM-D) score of up to 17.<ref>C. Randløv, J. Mehlsen, C.F. Thomsen, C. Hedman, H. von Fircks and K. Winther. "The efficacy of St. John's Wort in patients with minor depressive symptoms or dysthymia - a double-blind placebo-controlled study" ''Phytomedicine''. 2006 March; '''13'''(4): 215–221. PMID 16423519.</ref>
====Evidence against efficacy for Major Depressive Disorder====
A major study funded by the [[National Institutes of Health|NIH]] in the United States failed to find any evidence that Hypericum extract of St John's wort was effective in treating moderate to severe cases of major depression (Hypericum Depression Trial Study Group, 2002). This study involved 340 patients, diagnosed with Major Depressive Disorder based on [[DSM-IV]] criteria and assessed using [[Hamilton Depression Rating Scale]] (HAM-D) and [[Clinical Global Impression]] (CGI) scores. The trial was a multi-centre randomised double-blind placebo-controlled trial, comparing one preparation of St John's wort (Li 160) to the antidepressant [[sertraline]], and to placebo. No statisticallly significant effect was garnered from Li 160. Sertraline was also no better than placebo in this study, based on the primary outcome measure (the HAM-D).<ref>Hypericum Depression Trial Study Group (2002). [http://jama.ama-assn.org/cgi/content/abstract/287/14/1807 Effect of Hypericum perforatum (St John's Wort) in Major Depressive Disorder.] ''JAMA'' '''287''' (14), 1807-1814. PMID 11939866</ref>
===Pharmacology===
The exact mechanism by which St John's wort — and even conventional antidepressants — functions is unclear and subject to [[wiktionary:conjecture|conjecture]].
The St John's wort mechanism is believed to involve inhibition of [[Serotonin|serotonin (5-HT)]] reuptake, much like the conventional [[selective serotonin reuptake inhibitor]] (SSRI) antidepressants.
The major active antidepressive constituents in St John's wort are thought to be [[hyperforin]] and [[hypericin]], although other biologically active constituents present, for example, [[flavonoid]]s and [[tannin]]s, may also be involved.<ref>Nahrstedt A, Butterweck V (1997). Biologically active and other chemical constituents of the herb of Hypericum perforatum L. ''Pharmacopsychiatry'' '''30''' (Suppl 2), 129-34.</ref>
Some believe that [[hyperforin]] is the major constituent responsible for antidepressant activity, and it has been shown to inhibit the uptake of [[5-HT]], [[dopamine]], [[noradrenaline]], [[GABA]] and [[glutamate]].<ref>Chatterjee SS, Bhattacharya SK, Wonnemann M, Erdelmeier C (1998b). Antidepressant activity of hypericum perforatum and hyperforin: the neglected possibility. ''Pharmacopsychiatry'' '''31''' (Suppl 1), 7-15.</ref> On the other hand, a hyperforin free extract of St John's wort (Ze 117 - Remotiv) has been shown to have significant antidepressive effects.<ref name="woelk_et_al_2006" /><ref name="schrader_et_al_2000" /> Therefore current thinking is that the whole extract should be considered the "active ingredient" and that one or two constituents cannot explain the activity of the product.{{Fact|date=August 2007}}
===Dosage and formulations===
The dosage and content of St John's wort preparations vary greatly between formulations, because of variability in the plant source and preparation processes. The doses of St John’s wort extract used in clinical trials generally range from 350 to 1800 mg daily (equivalent to 0.4 to 2.7 mg hypericin depending on the preparation).<ref name="linde_mulrow_2003" /> Because of the variable nature of herbal medicines, the clinical trial results using one product cannot be extrapolated to other products containing the same herb (just as a prize winning wine is not the same as everything else made from grapes). Only a handful of products made from St John's wort have been used in clinical studies (for example, Li 160 and Ze 117).
The recommended dosage for various forms of St John's wort as recommended by the British Herbal Medicine Association Scientific Committee (1983){{Fact|date=February 2007}} are as follows:
*dried herb: 2-4 g or by infusion three times daily
*liquid extract 2-4 mL (1:1 in 25% alcohol) three times daily
*tincture 2-4mL (1:10 in 45% alcohol) three times daily
In markets where standardised extracts are not available, the content of marketed products can vary widely. Some brands of over-the-counter St John's wort can have a totally different chemical profile than others. The same can even be true of two dosage units from different batches of the same brand. Even where extracts are standardised it is debatable whether using [[hypericin]] as the standard is useful, since other constituents including [[hyperforin]] are biologically active.
As with other antidepressants, Hypericum should be taken for at least four weeks before its effectiveness can be properly assessed.
==Other medical uses==
In addition to antidepressant, there are other medical uses for St John's wort:
It may also decrease alcohol intake. discovered that [[hyperforin]], (found in the plant), appears to be the reason why.<ref> [http://altmedicine.about.com/od/herbsupplementguide/a/herbs_alcohol.htm UK Bradford School of Pharmacy] </ref>
The aerial parts of the plant can be cut and dried for later use in the form of [[herbal tea]] with pleasant, though somewhat bitter, taste and for its medicinal properties.
Hyperforin, a major constituent, has also been found to have excellent antibacterial properties; in ultrapurified form a concentration of 0.1 mg/ml kills [[methicillin]]-resistant forms of ''[[Staphylococcus aureus]]'' (MRSA).<ref>[http://www.wissenschaft-online.de/artikel/342746 wissenschaft-online.de] (in German)</ref>
==Adverse effects==
St John's wort is generally well tolerated, with an adverse effect profile similar to [[placebo]].<ref name="ernst_et_al_1998">Ernst E, Rand JI, Barnes J, Stevinson C (1998). Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). ''Eur J Clin Pharmacol'' '''54''' (8), 589-94.</ref> The most common adverse effects reported are gastrointestinal symptoms, dizziness, confusion, tiredness and sedation.<ref>Barnes J, Anderson LA, Phillipson JD (2002). ''Herbal Medicines: A guide for healthcare professionals'' (2 ed.) London: Pharmaceutical Press. ISBN 0-85369-474-5.</ref>
St John's wort may rarely cause [[photodermatitis|photosensitivity]]. This can lead to visual sensitivity to light and to sunburns in situations that would not normally cause them.<ref name="ernst_et_al_1998" />
Some research shows that St John's wort may adversely affect fertility in both men and women.<ref>Stahl, SM (2000). Essential psychopharmacology: neuroscientific basis and practical applications, Cambridge: Cambridge University Press, 2nd ed, page 266.</ref>
St John's wort has been known to instigate mania in [[bipolar disorder|bipolar]] patients and for these people it should be used with caution, just as with any anti-depressant.<ref>http://bipolar.about.com/cs/menu_nutrition/a/0011_stjohns.htm</ref><ref>http://www.pendulum.org/treatments.htm</ref>
Caution is also recommended{{who|date=November 2007}} when discontinuing use.
Besides, there are many drug interactions of St John's Wort, inducing or inhibiting the effects of other medications:
==Drug interactions==
===Pharmacokinetic interactions===
St John's wort has been shown to cause multiple drug interactions mainly through [[Enzyme induction and inhibition|induction]] of the [[cytochrome P450]] enzyme [[CYP3A4]], but also [[CYP2C9]]. This results in the increased metabolism of those drugs, resulting in decreased concentration and clinical effect. The principal constituent thought to be responsible is [[hyperforin]].
<center>
{| class="wikitable"
|+'''Examples of drugs causing clinically-significant interactions with St John's wort'''
|-
!Class
!Drugs
|-
|[[antiepileptic]]s
|[[carbamazepine]], [[phenytoin]]
|-
|[[antiretroviral]]s
|[[non-nucleoside reverse transcriptase inhibitor]]s, [[protease inhibitor]]s
|-
|[[benzodiazepine]]s
|[[alprazolam]], [[midazolam]]
|-
|[[hormonal contraception]]
|[[Oral contraceptive formulations#Combined oral contraceptive pills|combined oral contraceptive]]s
|-
|[[immunosuppressant]]s
|[[calcineurin inhibitor]]s, [[ciclosporin]], [[tacrolimus]]
|-
|others
|[[digoxin]], [[methadone]], [[omeprazole]], [[phenobarbitone]], [[theophylline]], [[warfarin]], [[levodopa]]
|-
| colspan="2" | <small>Reference: Rossi, 2005</small>
|}
</center>
For complete list, see [[CYP3A4#CYP3A4 ligands]] and [[CYP2C9#CYP2C9 Ligands]]. For further updating on interactions and appropriate management, see [http://www.herbological.com/images/SJW_table.pdf Herbological.com - S:t John's Wort Interactions table].
====Contraceptives====
St John's wort may interact with birth control pills and may reduce the effectiveness of oral contraceptives. However, while breakthrough bleeding was observed to occur in the Swedish MPA study (the sample size of 8 women was small enough that the effect could not be differentiated from common breakthrough bleeding), no cases of pregnancy due to contraceptive/St John's wort interactions have been found in the literature despite over 20 years of widespread prescription in Germany.<ref>http://www.herbological.com/images/downloads/SJW.pdf</ref><ref>{{cite journal |last=Pfrunder |first=Arabelle |coauthors=Monika Schiesser, Simone Gerber, Manuel Haschke, Johannes Bitzer, Juergen Drewe |year=2003 |month=December |title=Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial |journal=British Journal of Clinical Pharmacology |volume=56 |issue=6 |pages=683-690 |doi=10.1046/j.1365-2125.2003.02005.x |url=http://www.blackwell-synergy.com/links/doi/10.1046/j.1365-2125.2003.02005.x/abs/ |accessdate=February 3, 2007 }}</ref><ref>{{cite journal |last=Schwarz |first=Ute I. |coauthors=Barbara Büschel, W. Kirch |year=2003 |title=Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception |journal=British Journal of Clinical Pharmacology |volume=55 |issue=1 |year=2003 |month=January |pages=112-113 |doi=10.1046/j.1365-2125.2003.01716.x |url=http://www.blackwell-synergy.com/links/doi/10.1046/j.1365-2125.2003.01716.x/full/?cookieSet=1 |accessdate=February 3, 2007 }}</ref>
===Pharmacodynamic interactions===
St John's wort may also contribute to [[serotonin syndrome]] in combination with other drugs which may elevate [[5-HT]] (serotonin) levels in the [[central nervous system]] (CNS).<ref>Rossi S (Ed.) (2005). ''[[Australian Medicines Handbook]] 2005''. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-9-3.</ref>
<center>
{| class="wikitable"
|+'''Drugs which may contribute to serotonin syndrome with St John's wort'''
|-
!Class
!Drugs
|-
|[[antidepressant]]s
|[[MAOI]]s, [[Tricyclic antidepressant|TCA]]s, [[SSRI]]s, [[mirtazapine]], [[venlafaxine]]
|-
|[[opioid]]s
|[[tramadol]], [[pethidine]]
|-
|CNS [[stimulant]]s
|[[phentermine]], [[diethylpropion]], [[amphetamine]]s, [[sibutramine]]
|-
|[[5-HT receptor|5-HT<sub>1</sub>]] agonists
|[[triptan]]s
|-
|illicit drugs
|[[methylenedioxymethamphetamine]] (MDMA), [[lysergic acid diethylamide]] (LSD), [[cocaine]]
|-
|others
|[[selegiline]], [[tryptophan]], [[buspirone]], [[Lithium pharmacology|lithium]], [[linezolid]], [[dextromethorphan]], [[5-HTP]]
|-
| colspan="2" | <small>Reference: Rossi, 2005</small>
|}
</center>
===History===
The first recorded use of ''Hypericum'' for medicinal purposes dates back to [[ancient Greece]], and it has been used ever since. Hypericum was also used by [[Indigenous peoples of the Americas|Native Americans]] internally as an [[abortifacient]] and externally as an [[anti-inflammatory]], [[astringent]], and [[antiseptic]].
Its use as a[[herbal tea]] has long been enjoyed.
The flowers and stems of St John's wort have also been used to produce red and yellow [[dye]]s.
== References ==
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==Further reading==
*British Herbal Medicine Association Scientific Committee (1983). ''British Herbal Pharmacopoeia''. West Yorkshire: British Herbal Medicine Association. ISBN 0-903032-07-4
==See also==
* [[Dietary supplement]]
* EU [[Food supplements directive]]
== External links ==
*[http://www.quackwatch.org/01QuackeryRelatedTopics/DSH/stjohn.html QuackWatch article on St John's wort] Criticism of the use of S. John's wort to treat depression. Includes [[Food and Drug Administration]] (FDA) warnings about interference with treatments for heart disease, some cancers, AIDS and others.
{{wikispecies|Hypericum}}
{{Commons|Hypericum perforatum}}
[[Category:Abortifacients]]
[[Category:Clusiaceae]]
[[Category:Flora of Europe]]
[[Category:Flora of Estonia]]
[[Category:Flora of the United Kingdom]]
[[Category:Medicinal plants]]
[[Category:Plants poisonous to equines]]
| color = lightgreen
| name = St John's wort
| image = Saint johns wart flowers.jpg
| image_width = 250px
| regnum = [[Plant]]ae
| divisio = [[Flowering plant|Magnoliophyta]]
| classis = [[Dicotyledon|Magnoliopsida]]
| ordo = [[Malpighiales]]
| familia = [[Clusiaceae]]
| genus = ''[[Hypericum]]''
| species = '''''H. perforatum'''''
| binomial = ''Hypericum perforatum''
| binomial_authority = [[Carolus Linnaeus|L.]]
}}
'''St John's wort''' ([[International Phonetic Alphabet|IPA pronunciation]]: [[General American]] {{IPA|[-wɝt]}}, [[Received Pronunciation]] {{IPA|[wɜːt]}}, rhyming with ''fort'') used alone refers to the species ''Hypericum perforatum'', also known as '''Tipton's Weed''' or '''Klamath weed''', but, with qualifiers, is used to refer to any species of the genus ''[[Hypericum]]''. Therefore, ''H. perforatum'' is sometimes called '''Common St John's wort''' to differentiate it. The species of ''Hypericum'' have been placed by some in the family [[Hypericaceae]], but more recently have been included in the [[Clusiaceae]].{{Fact|date=February 2007}} Approximately 370 species of the genus ''Hypericum'' exist worldwide with a native geographical distribution including temperate and subtropical regions of North America, Europe, Asia Minor, Russia, India and China.
==The plant==
''Hypericum perforatum'' is a yellow-flowering, [[rhizome|rhizomatous]], [[perennial plant|perennial]] [[herb]] indigenous to Europe, which has been introduced to the Americas and grows wild in many meadows. The common name comes from its traditional flowering and harvesting on [[John the Baptist|St John's]] day, [[24 June]]. The [[genus]] name ''Hypericum'' is derived from the Greek words ''hyper'' (above) and ''eikon'' (picture), in reference to the traditional use of the plant to ward off evil, by hanging plants over a picture in the house during St John's day. The [[species]] name ''perforatum'' refers to the presence of small oil glands in the leaves that look like windows, which can be seen when they are held against the light.
Although ''Hypericum perforatum'' is grown commercially in some regions of south east Europe, it is listed as a noxious weed in more than twenty countries. In pastures, St John’s wort acts as both a toxic and invasive weed.<ref>http://www.northwestweeds.nsw.gov.au/st_johns_wort.htm</ref> It replaces useful vegetation to the extent of making productive land unviable or acts as an alien species in natural ecosystems. Ingestion by livestock can cause photosensitization, central nervous system depression, spontaneous abortion, and can lead to death. Effective herbicides for control of ''Hypericum'' include [[2,4-D]], picloram, and [[glyphosate]]. In western [[North America]] three beetles ''[[Chrysolina quadrigemina]]'', ''[[Chrysolina hyperici]]'' and ''[[Agrilus hyperici]]'' have been introduced as [[biocontrol]] agents.
==Identification==
St John’s wort can be visually recognized by leaf and flower type. Yellow, five petaled flowers approximately 20 mm across occur between late Spring and early to mid Summer. Leaves exhibit obvious translucent dots when held up to the light, giving them a ‘perforated’ appearance, hence the plant's Latin name. When flowers or seed pods are crushed, a reddish/purple liquid is produced.
[[Image:StJohnswortID.jpg|right|thumb|''The translucent dots on the St John's wort leaves'']]
==Botanical description==
St John's wort is a [[perennial plant]] with extensive, creeping [[rhizomes]]. <!-- barren shoots prostrate | QUESTION: not sure what this means or how to turn it into a sentence--> Its stems are erect, branched in the upper section, and can grow to 1 m high. It has opposing, stalkless, narrow, oblong leaves which are 12 mm long or slightly larger. The leaves are yellow-green in color, with transparent dots throughout the tissue and occasionally with a few black dots on the lower surface. Its flowers measure up to 2.5 cm across, have five petals, and are colored bright yellow with conspicuous black dots. The flowers appear in broad [[inflorescence|cymes]] at the ends of the upper branches. The [[sepals]] are pointed, with glandular dots in the tissue. There are many [[stamens]], which are united at the base into three bundles.
==Ecology==
St John’s wort has a complex life cycle that includes a mature plant cycle with vegetative and sexual reproduction. It thrives in areas with either a winter- or summer-dominant rainfall pattern; however, distribution is restricted by temperatures too low for seed germination or seedling survival. Altitudes greater than 1500 m, rainfall less than 500 mm, and a daily mean January temperature greater than 24 degrees are considered limiting thresholds. Depending on environmental and climatic conditions, and rosette age, St John’s wort will alter growth form and habit to promote survival. Summer rains are particularly effective in allowing the plant to grow vegetatively, following defoliation by insects or grazing.
== Hypericum poisoning (livestock) ==
===Clinical signs===
At large doses, St John's wort is [[poison]]ous to grazing [[livestock]] (cattle, sheep, goats, horses).<ref>http://www.northwestweeds.nsw.gov.au/st_johns_wort.htm</ref> Behavioural signs of poisoning are general restlessness and skin irritation. Restlessness is often indicated by pawing of the ground, head shaking, 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 graziers include the appearance of circular patches giving hillsides a ‘crop circle’ appearance, possibly from this phenomenon. Animals typically seek shade and have reduced appetite. 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 [[Abortion|abort]]. Lesions on [[udder]]s are often apparent. Horses may show signs of [[Anorexia (symptom)|anorexia]], [[Depression (mood)|depression]] (with a comatose state), dilated pupils, and injected [[conjunctiva]].
===Early 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 more affected than old animals. In severe cases death may occur, as a direct result of starvation, or because of secondary disease or [[Sepsis|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 the milk production, or the transmission of a toxin in the milk.
===Photosensitisation===
Most clinical signs are caused by [[Photosensitivity|photosensitisation]].<ref>http://www.northwestweeds.nsw.gov.au/st_johns_wort.htm#effect_on_animals</ref> Plants may induce either primary or secondary photosensitisation: primary photosensitisation directly from chemicals contained in ingested plants, or 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 Hypericum-related effect on the excretory capacity of the liver, or any interference was minimal and temporary. However, at high and continuous dose rates changes in blood plasma indicative of some liver damage have been observed.
Photosensitisation causes skin inflammation by a mechanism involving a pigment or photodynamic compound, which when activated by a certain wavelength of light leads to [[Redox|oxidation]] reactions [[in vivo]]. This leads to lesions of tissue, particularly noticeable on and around parts of skin exposed to light. Lightly covered or poorly [[Biological pigment|pigment]]ed areas are most conspicuous. Removal of affected animals from sunlight results in reduced symptoms of poisoning.
==Use as Antidepressant==
In modern medicine, standardized ''Hypericum'' extract (obtained from ''H. perforatum'') is commonly used as a treatment for [[Clinical depression|depression]] and [[anxiety disorder]]s. In [[homeopathy]], ''Hypericum'' is used in the treatment of numerous medical problems, yet the rate of success has not been adequately documented.
St John's wort is today most widely known as a herbal treatment for [[Clinical depression|depression]]. In some countries, such as [[Germany]], it is commonly prescribed for mild depression, especially in children, adolescents, and where cost is a concern.<ref>Fegert J, Kölch M, Zito J, Gaeske G, Janhsen K (2006). [http://www.liebertonline.com/doi/abs/10.1089/cap.2006.16.197 Antidepressant Use in Children and Adolescents in Germany]. Journal of Child and Adolescent Psychopharmacology 16, 197-206.</ref> Standardized extracts are generally available [[Over-the-counter drug|over the counter]] – however, in some countries (such as [[Ireland]]) a prescription is required. Extracts are usually in [[tablet]] or [[encapsulation (pharmacology)|capsule]] form, and also in teabags and [[tincture]]s.
===Clinical evidence===
[[Image:Hypericum perforatum plantlets.jpg|thumb|250px|Seedlings of St John's wort]]
Clinical studies of St John's wort preparations have mainly focused on the efficacy of the herb in [[clinical depression]]. Several studies and [[meta-study|meta-analyses]] have found it to be effective in the treatment of mild to moderate depression, with fewer side effects than many conventional [[antidepressant]]s. Other studies, including a major NIH study that focused on moderate to severe depression, have shown no improvements.<ref>Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. Journal of the American Medical Association. 2002;287(14):1807–1814.</ref>
====Evidence for efficacy====
An early [[meta-study]] indicated that extracts of ''Hypericum'' may be more efficacious than placebo for the treatment of mild to moderately severe depressive disorders.<ref>Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D (1996). [http://bmj.bmjjournals.com/cgi/content/full/313/7052/253?view=full&pmid=8704532 St John’s wort for depression – an overview and meta-analysis of randomised clinical trials.] ''Br Med J'' '''313''', 253–258.</ref> This study, which covered the results from 23 smaller, earlier studies, is perhaps the most often cited by manufacturers and other supporters of St John's wort.
This study was later updated to include further studies, for a total of 27, to form a [[Cochrane Library|Cochrane Review]]. The updated review found that ''Hypericum'' preparations were significantly superior to placebo ([[rate ratio]] 2.47; 95% [[confidence interval]] 1.69 to 3.61) and similarly effective as standard antidepressants (single preparations 1.01; 0.87 to 1.16, combinations 1.52; 0.78 to 2.94).<ref name="linde_mulrow_2003">Linde K, Mulrow CD (2003). St John's wort for depression (Cochrane Review). In: ''The Cochrane Library'', Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.</ref>
Another meta-analysis, with stricter inclusion criteria, found that ''Hypericum'' was more efficacious than placebo; and as efficacious as [[tricyclic antidepressant]]s, with fewer adverse drug reactions.<ref>Kim HL, Streltzer J, Goebert D (1999). St. John's wort for Depression: A Meta-Analysis of Well-Defined Clinical Trials. ''J Ment Nerv Dis'' '''187''' (9), 532-538.</ref> This meta-analysis showed that the [[response rate]] for St John’s wort was significantly greater than that for placebo (73.2 versus 37.9%, respectively, [[relative risk]] 1.48 and 95% [[Confidence interval|CI]] 1.03–1.92) and similar to that observed with tricyclic antidepressants (64 versus 66.4% for St John’s wort and tricyclic antidepressants, respectively, relative risk 1.11 and 95% CI 0.92–1.29).
Other, more recent trials have also shown greater efficacy than placebo, and comparable efficacy to standard antidepressants with a superior adverse effect profile<!-- In English, please. -->.<ref name="woelk_et_al_2006">Woelk H, ''et al.'' (2000). Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. ''Br Med J'' '''321''', 536-9.</ref><ref name="schrader_et_al_2000">Schrader E, ''et al.'' (2000). Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomised, controlled study in mild-moderate depression. ''Int Clin Psychopharmacology'' '''15''', 61-68.</ref><ref>Laakmann G, Schule C, Baghai T, Kieser M (1998). St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. ''Pharmacopsychiatry'' '''31''' (Suppl 1), 54-9.</ref><ref>Harrer G, Schmidt U, Kuhn U, Biller A (1999). Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine. ''Arzneimittelforschung'' '''49''' (4), 289-96.</ref><ref>Philipp M, Kohnen R, Hiller KO (1999). Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. ''Br Med J'' '''319''' (7224), 1534-8.</ref><ref>{{cite journal | author=Szegedi A, Kohnen R, Dienel A, Kieser M | title=Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine | journal=BMJ | year=2005 | volume=330 | issue=7490 | pages=503–506 | url=http://bmj.bmjjournals.com/cgi/content/abstract/330/7490/503 }}</ref><ref>Lecrubier ''et al.'' "Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial." ''Am J Psychiatry''. 2002 Aug;159(8):1361-6. PMID 12153829 </ref>
Additionally, a 2006 study involving 150 patients with minor depressive symptoms or [[dysthymia]] found that St John's wort has a clinically significant effect in patients with minor depression, but not those suffering from dysthymia. It was concluded that St John's wort can be effective in the treatment of people with minor depression with a [[Hamilton Depression Rating Scale|Hamilton Depression Scale]] for Depression (HAM-D) score of up to 17.<ref>C. Randløv, J. Mehlsen, C.F. Thomsen, C. Hedman, H. von Fircks and K. Winther. "The efficacy of St. John's Wort in patients with minor depressive symptoms or dysthymia - a double-blind placebo-controlled study" ''Phytomedicine''. 2006 March; '''13'''(4): 215–221. PMID 16423519.</ref>
====Evidence against efficacy for Major Depressive Disorder====
A major study funded by the [[National Institutes of Health|NIH]] in the United States failed to find any evidence that Hypericum extract of St John's wort was effective in treating moderate to severe cases of major depression (Hypericum Depression Trial Study Group, 2002). This study involved 340 patients, diagnosed with Major Depressive Disorder based on [[DSM-IV]] criteria and assessed using [[Hamilton Depression Rating Scale]] (HAM-D) and [[Clinical Global Impression]] (CGI) scores. The trial was a multi-centre randomised double-blind placebo-controlled trial, comparing one preparation of St John's wort (Li 160) to the antidepressant [[sertraline]], and to placebo. No statisticallly significant effect was garnered from Li 160. Sertraline was also no better than placebo in this study, based on the primary outcome measure (the HAM-D).<ref>Hypericum Depression Trial Study Group (2002). [http://jama.ama-assn.org/cgi/content/abstract/287/14/1807 Effect of Hypericum perforatum (St John's Wort) in Major Depressive Disorder.] ''JAMA'' '''287''' (14), 1807-1814. PMID 11939866</ref>
===Pharmacology===
The exact mechanism by which St John's wort — and even conventional antidepressants — functions is unclear and subject to [[wiktionary:conjecture|conjecture]].
The St John's wort mechanism is believed to involve inhibition of [[Serotonin|serotonin (5-HT)]] reuptake, much like the conventional [[selective serotonin reuptake inhibitor]] (SSRI) antidepressants.
The major active antidepressive constituents in St John's wort are thought to be [[hyperforin]] and [[hypericin]], although other biologically active constituents present, for example, [[flavonoid]]s and [[tannin]]s, may also be involved.<ref>Nahrstedt A, Butterweck V (1997). Biologically active and other chemical constituents of the herb of Hypericum perforatum L. ''Pharmacopsychiatry'' '''30''' (Suppl 2), 129-34.</ref>
Some believe that [[hyperforin]] is the major constituent responsible for antidepressant activity, and it has been shown to inhibit the uptake of [[5-HT]], [[dopamine]], [[noradrenaline]], [[GABA]] and [[glutamate]].<ref>Chatterjee SS, Bhattacharya SK, Wonnemann M, Erdelmeier C (1998b). Antidepressant activity of hypericum perforatum and hyperforin: the neglected possibility. ''Pharmacopsychiatry'' '''31''' (Suppl 1), 7-15.</ref> On the other hand, a hyperforin free extract of St John's wort (Ze 117 - Remotiv) has been shown to have significant antidepressive effects.<ref name="woelk_et_al_2006" /><ref name="schrader_et_al_2000" /> Therefore current thinking is that the whole extract should be considered the "active ingredient" and that one or two constituents cannot explain the activity of the product.{{Fact|date=August 2007}}
===Dosage and formulations===
The dosage and content of St John's wort preparations vary greatly between formulations, because of variability in the plant source and preparation processes. The doses of St John’s wort extract used in clinical trials generally range from 350 to 1800 mg daily (equivalent to 0.4 to 2.7 mg hypericin depending on the preparation).<ref name="linde_mulrow_2003" /> Because of the variable nature of herbal medicines, the clinical trial results using one product cannot be extrapolated to other products containing the same herb (just as a prize winning wine is not the same as everything else made from grapes). Only a handful of products made from St John's wort have been used in clinical studies (for example, Li 160 and Ze 117).
The recommended dosage for various forms of St John's wort as recommended by the British Herbal Medicine Association Scientific Committee (1983){{Fact|date=February 2007}} are as follows:
*dried herb: 2-4 g or by infusion three times daily
*liquid extract 2-4 mL (1:1 in 25% alcohol) three times daily
*tincture 2-4mL (1:10 in 45% alcohol) three times daily
In markets where standardised extracts are not available, the content of marketed products can vary widely. Some brands of over-the-counter St John's wort can have a totally different chemical profile than others. The same can even be true of two dosage units from different batches of the same brand. Even where extracts are standardised it is debatable whether using [[hypericin]] as the standard is useful, since other constituents including [[hyperforin]] are biologically active.
As with other antidepressants, Hypericum should be taken for at least four weeks before its effectiveness can be properly assessed.
==Other medical uses==
In addition to antidepressant, there are other medical uses for St John's wort:
It may also decrease alcohol intake. discovered that [[hyperforin]], (found in the plant), appears to be the reason why.<ref> [http://altmedicine.about.com/od/herbsupplementguide/a/herbs_alcohol.htm UK Bradford School of Pharmacy] </ref>
The aerial parts of the plant can be cut and dried for later use in the form of [[herbal tea]] with pleasant, though somewhat bitter, taste and for its medicinal properties.
Hyperforin, a major constituent, has also been found to have excellent antibacterial properties; in ultrapurified form a concentration of 0.1 mg/ml kills [[methicillin]]-resistant forms of ''[[Staphylococcus aureus]]'' (MRSA).<ref>[http://www.wissenschaft-online.de/artikel/342746 wissenschaft-online.de] (in German)</ref>
==Adverse effects==
St John's wort is generally well tolerated, with an adverse effect profile similar to [[placebo]].<ref name="ernst_et_al_1998">Ernst E, Rand JI, Barnes J, Stevinson C (1998). Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). ''Eur J Clin Pharmacol'' '''54''' (8), 589-94.</ref> The most common adverse effects reported are gastrointestinal symptoms, dizziness, confusion, tiredness and sedation.<ref>Barnes J, Anderson LA, Phillipson JD (2002). ''Herbal Medicines: A guide for healthcare professionals'' (2 ed.) London: Pharmaceutical Press. ISBN 0-85369-474-5.</ref>
St John's wort may rarely cause [[photodermatitis|photosensitivity]]. This can lead to visual sensitivity to light and to sunburns in situations that would not normally cause them.<ref name="ernst_et_al_1998" />
Some research shows that St John's wort may adversely affect fertility in both men and women.<ref>Stahl, SM (2000). Essential psychopharmacology: neuroscientific basis and practical applications, Cambridge: Cambridge University Press, 2nd ed, page 266.</ref>
St John's wort has been known to instigate mania in [[bipolar disorder|bipolar]] patients and for these people it should be used with caution, just as with any anti-depressant.<ref>http://bipolar.about.com/cs/menu_nutrition/a/0011_stjohns.htm</ref><ref>http://www.pendulum.org/treatments.htm</ref>
Caution is also recommended{{who|date=November 2007}} when discontinuing use.
Besides, there are many drug interactions of St John's Wort, inducing or inhibiting the effects of other medications:
==Drug interactions==
===Pharmacokinetic interactions===
St John's wort has been shown to cause multiple drug interactions mainly through [[Enzyme induction and inhibition|induction]] of the [[cytochrome P450]] enzyme [[CYP3A4]], but also [[CYP2C9]]. This results in the increased metabolism of those drugs, resulting in decreased concentration and clinical effect. The principal constituent thought to be responsible is [[hyperforin]].
<center>
{| class="wikitable"
|+'''Examples of drugs causing clinically-significant interactions with St John's wort'''
|-
!Class
!Drugs
|-
|[[antiepileptic]]s
|[[carbamazepine]], [[phenytoin]]
|-
|[[antiretroviral]]s
|[[non-nucleoside reverse transcriptase inhibitor]]s, [[protease inhibitor]]s
|-
|[[benzodiazepine]]s
|[[alprazolam]], [[midazolam]]
|-
|[[hormonal contraception]]
|[[Oral contraceptive formulations#Combined oral contraceptive pills|combined oral contraceptive]]s
|-
|[[immunosuppressant]]s
|[[calcineurin inhibitor]]s, [[ciclosporin]], [[tacrolimus]]
|-
|others
|[[digoxin]], [[methadone]], [[omeprazole]], [[phenobarbitone]], [[theophylline]], [[warfarin]], [[levodopa]]
|-
| colspan="2" | <small>Reference: Rossi, 2005</small>
|}
</center>
For complete list, see [[CYP3A4#CYP3A4 ligands]] and [[CYP2C9#CYP2C9 Ligands]]. For further updating on interactions and appropriate management, see [http://www.herbological.com/images/SJW_table.pdf Herbological.com - S:t John's Wort Interactions table].
====Contraceptives====
St John's wort may interact with birth control pills and may reduce the effectiveness of oral contraceptives. However, while breakthrough bleeding was observed to occur in the Swedish MPA study (the sample size of 8 women was small enough that the effect could not be differentiated from common breakthrough bleeding), no cases of pregnancy due to contraceptive/St John's wort interactions have been found in the literature despite over 20 years of widespread prescription in Germany.<ref>http://www.herbological.com/images/downloads/SJW.pdf</ref><ref>{{cite journal |last=Pfrunder |first=Arabelle |coauthors=Monika Schiesser, Simone Gerber, Manuel Haschke, Johannes Bitzer, Juergen Drewe |year=2003 |month=December |title=Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial |journal=British Journal of Clinical Pharmacology |volume=56 |issue=6 |pages=683-690 |doi=10.1046/j.1365-2125.2003.02005.x |url=http://www.blackwell-synergy.com/links/doi/10.1046/j.1365-2125.2003.02005.x/abs/ |accessdate=February 3, 2007 }}</ref><ref>{{cite journal |last=Schwarz |first=Ute I. |coauthors=Barbara Büschel, W. Kirch |year=2003 |title=Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception |journal=British Journal of Clinical Pharmacology |volume=55 |issue=1 |year=2003 |month=January |pages=112-113 |doi=10.1046/j.1365-2125.2003.01716.x |url=http://www.blackwell-synergy.com/links/doi/10.1046/j.1365-2125.2003.01716.x/full/?cookieSet=1 |accessdate=February 3, 2007 }}</ref>
===Pharmacodynamic interactions===
St John's wort may also contribute to [[serotonin syndrome]] in combination with other drugs which may elevate [[5-HT]] (serotonin) levels in the [[central nervous system]] (CNS).<ref>Rossi S (Ed.) (2005). ''[[Australian Medicines Handbook]] 2005''. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-9-3.</ref>
<center>
{| class="wikitable"
|+'''Drugs which may contribute to serotonin syndrome with St John's wort'''
|-
!Class
!Drugs
|-
|[[antidepressant]]s
|[[MAOI]]s, [[Tricyclic antidepressant|TCA]]s, [[SSRI]]s, [[mirtazapine]], [[venlafaxine]]
|-
|[[opioid]]s
|[[tramadol]], [[pethidine]]
|-
|CNS [[stimulant]]s
|[[phentermine]], [[diethylpropion]], [[amphetamine]]s, [[sibutramine]]
|-
|[[5-HT receptor|5-HT<sub>1</sub>]] agonists
|[[triptan]]s
|-
|illicit drugs
|[[methylenedioxymethamphetamine]] (MDMA), [[lysergic acid diethylamide]] (LSD), [[cocaine]]
|-
|others
|[[selegiline]], [[tryptophan]], [[buspirone]], [[Lithium pharmacology|lithium]], [[linezolid]], [[dextromethorphan]], [[5-HTP]]
|-
| colspan="2" | <small>Reference: Rossi, 2005</small>
|}
</center>
===History===
The first recorded use of ''Hypericum'' for medicinal purposes dates back to [[ancient Greece]], and it has been used ever since. Hypericum was also used by [[Indigenous peoples of the Americas|Native Americans]] internally as an [[abortifacient]] and externally as an [[anti-inflammatory]], [[astringent]], and [[antiseptic]].
Its use as a[[herbal tea]] has long been enjoyed.
The flowers and stems of St John's wort have also been used to produce red and yellow [[dye]]s.
== References ==
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==Further reading==
*British Herbal Medicine Association Scientific Committee (1983). ''British Herbal Pharmacopoeia''. West Yorkshire: British Herbal Medicine Association. ISBN 0-903032-07-4
==See also==
* [[Dietary supplement]]
* EU [[Food supplements directive]]
== External links ==
*[http://www.quackwatch.org/01QuackeryRelatedTopics/DSH/stjohn.html QuackWatch article on St John's wort] Criticism of the use of S. John's wort to treat depression. Includes [[Food and Drug Administration]] (FDA) warnings about interference with treatments for heart disease, some cancers, AIDS and others.
{{wikispecies|Hypericum}}
{{Commons|Hypericum perforatum}}
[[Category:Abortifacients]]
[[Category:Clusiaceae]]
[[Category:Flora of Europe]]
[[Category:Flora of Estonia]]
[[Category:Flora of the United Kingdom]]
[[Category:Medicinal plants]]
[[Category:Plants poisonous to equines]]
