St John's wort
Scientific classification
Kingdom: Plantae Division: Magnoliophyta Class: Magnoliopsida Order: Malpighiales Family: Clusiaceae Genus: Hypericum Species: H. Plants are living Organisms belonging to the kingdom Plantae. The flowering plants or angiosperms ( Angiospermae or Magnoliophyta) are the most widespread group Dicotyledons, or "dicots", is a name for a group of Flowering plants whose Seed typically has two embryonic leaves or Cotyledons There The Malpighiales are a large order of Flowering plants included in the group named Eurosids I in the recent APG classification The Clusiaceae or Guttiferae Juss (1789 ( nom alt et cons = alternative and valid name is a family of Plants including Hypericum is a Genus of about 400 Species of Flowering plants in the family Clusiaceae, Subfamily Hypericoideae perforatum
Binomial name
Hypericum perforatum L.

St John's wort (pronounced IPA: /sɪndʒənsˈwɝt/) 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. Carl Linnaeus (Latinized as Carolus Linnaeus, also known after his ennoblement as, May 23 new style (13 May old style 1707 who laid the foundations for Hypericum is a Genus of about 400 Species of Flowering plants in the family Clusiaceae, Subfamily Hypericoideae 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. The Clusiaceae or Guttiferae Juss (1789 ( nom alt et cons = alternative and valid name is a family of Plants including The Clusiaceae or Guttiferae Juss (1789 ( nom alt et cons = alternative and valid name is a family of Plants including 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.

Contents 1 The plant 2 Identification 3 Botanical description 4 Chemical composition 5 Ecology 6 Hypericum poisoning (livestock) 6.1 Clinical signs 6.2 Early diagnosis 6.3 Photosensitisation 7 Use as spice 8 Use as antidepressant 8.1 Clinical evidence 8.1.1 Evidence for efficacy 8.1.2 Evidence against efficacy for Major Depressive Disorder 8.2 Pharmacology 9 Other medical uses 10 Adverse effects 11 Drug interactions 11.1 Pharmacokinetic interactions 11.1.1 Contraceptives 11.2 Pharmacodynamic interactions 11.3 History 12 References 13 Further reading 14 See also 15 External links

The plant

Hypericum perforatum is a yellow-flowering, rhizomatous, perennial herb indigenous to Europe, which has been introduced to the Americas and grows wild in many meadows. In Botany, a rhizome is a horizontal stem of a Plant that is usually found underground often sending out Roots and Shoots A perennial plant or perennial ( Latin per, "through" annus, "year" is a Plant that lives for more than A(n herb (ˈhɝb or /ˈɝb/ see pronunciation differences) is a plant that is valued for qualities such as medicinal properties flavor scent or the like The common name comes from its traditional flowering and harvesting on St John's day, 24 June. Saint John the Baptist ( heb. Jochanan ben Sacharja, arab. يحيى Yaḥyā or يوحنا Yūḥanna, aram. Events 972 - Battle of Cedynia, the first documented victory of Polish forces takes place 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. A genus (plural genera from Γένος Latin genus "descent family type gender" is a low-level Taxonomic 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. In Biology, a species is one of the basic units of Biological classification and a Taxonomic rank.

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. ^[1] 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. 24-Dichlorophenoxyacetic acid (24-D is a common systemic Herbicide used in the control of broadleaf weeds Glyphosate (N-(phosphonomethyl glycine is a non-selective Systemic Herbicide, absorbed through the leaves injected into the bole or applied to the stump of In western North America three beetles Chrysolina quadrigemina, Chrysolina hyperici and Agrilus hyperici have been introduced as biocontrol agents. Agrilus hyperici is a species of jewel beetle known by the common name St Biological control of pests in Agriculture is a method of controlling pests (including Insects Mites Weeds and plant diseases

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.

Botanical description

St John's wort is a perennial plant with extensive, creeping rhizomes. A perennial plant or perennial ( Latin per, "through" annus, "year" is a Plant that lives for more than In Botany, a rhizome is a horizontal stem of a Plant that is usually found underground often sending out Roots and Shoots 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 cymes at the ends of the upper branches. An inflorescence is a group or cluster of Flowers arranged on a stem that is composed of a main Branch or a complicated arrangement of branches The sepals are pointed, with glandular dots in the tissue. A sepal (from Latin separatus "separate" + petalum "petal" is a part of the flower of Angiosperms or flower plants There are many stamens, which are united at the base into three bundles. The stamen ( Plural stamina or stamens, from Latin stamen meaning "thread of the warp " is the male

Chemical composition

Herb and flowers contain different flavonoids (rutin, hyperoside, isoquercetin, quercitrin, quercetin, I3,II8-biapigenin, amentoflavone, astilbin, miquelianin). Hyperforin is one of the principal constituents identified in St John's wort. Hypericin is a red-coloured Anthraquinone -derivative which is together with Hyperforin one of the principal active constituents of Hypericum ( The term flavonoid (or bioflavonoid refers to a class of Plant Secondary metabolites According to the IUPAC nomenclature they can be classified into Rutin, also called rutoside, quercetin-3-rutinoside and sophorin, is a Citrus Flavonoid Glycoside found in Buckwheat Quercitrin is a Glycoside formed from the Flavonoid Quercetin and the Deoxy sugar Rhamnose. Quercetin is a Flavonoid and to be more specific a flavonol. It is the Aglycone form of a number of other flavonoid Glycosides, such as Phenolic acids (chlorogenic acid, 3-O-coumaroylquinic acid). Chlorogenic acid is a family of Esters formed between certain trans cinnamic acids and (-- Quinic acid and is a major phenolic compound Different naphtodianthrones (hypericin, pseudohypericin, protohypericin, protopseudohypericin), phloroglucinols (hyperforin, adhyperforin). Hypericin is a red-coloured Anthraquinone -derivative which is together with Hyperforin one of the principal active constituents of Hypericum ( Hyperforin is one of the principal constituents identified in St John's wort. And also essential oils (composed mainly of sesquiterpenes). The naphthodianthrones hypericin and pseudohypericin along with the Phloroglucinol derivative hyperforin are thought to be the active compontents.

^[2][3][4].

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 poisonous to grazing livestock (cattle, sheep, goats, horses). In the context of Biology, poisons are substances that can cause damage, Illness, or Death to Organisms usually by Livestock is the term used to refer (singularly or plurally to a Domesticated Animal intentionally reared in an agricultural setting to produce such as Food ^[5]

Behavioural signs of poisoning are general restlessness and skin irritation. New England is the name given to a region in the north of the state of New South Wales, Australia. 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. Foot-and-mouth disease ( FMD) or hoof-and-mouth disease ( Aphtae epizooticae) is a highly contagious and sometimes fatal viral 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. An Lesions on udders are often apparent. An Udder is the mammary organ of Female Cattle and some other Mammals including Goats and Sheep. Horses may show signs of anorexia, depression (with a comatose state), dilated pupils, and injected conjunctiva. Anorexia (deriving from the Greek "α(ν-" ( a(n-, a prefix that denotes absence + "όρεξη (orexe = appetite is the decreased sensation In the fields of Psychology and Psychiatry, the terms depression or depressed refer to both expected and pathologically chronic or severe The conjunctiva is a clear membrane that covers the Sclera (white part of the Eye) and lines the inside of the Eyelids It is made of lymphoid tissue

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 septicaemia of lesions. Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a Systemic inflammatory response syndrome or SIRS caused 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 photosensitisation. Photosensitivity is the amount to which an object reacts upon receiving Photons especially Visible light. ^[6] 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 oxidation reactions in vivo. Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state In vivo ( Latin: within the living means that which takes place inside an organism. This leads to lesions of tissue, particularly noticeable on and around parts of skin exposed to light. Lightly covered or poorly pigmented areas are most conspicuous. In Biology, a pigment or biochrome is any material resulting in Color of plant or animal cells which Removal of affected animals from sunlight results in reduced symptoms of poisoning.

Use as spice

St John's wort is sometimes used for flavouring distilled spirits.

Use as antidepressant

St John's wort is today most widely known as a herbal treatment for depression. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression In some countries, such as Germany, it is commonly prescribed for mild depression, especially in children, adolescents, and where cost is a concern. Germany, officially the Federal Republic of Germany ( ˈbʊndəsʁepuˌbliːk ˈdɔʏtʃlant is a Country in Central Europe. ^[7] Standardized extracts are generally available over the counter – however, in some countries (such as Ireland) a prescription is required. Over-the-counter (OTC drugs are medicines that may be sold without a prescription, in contrast to Prescription drugs The name "over-the-counter" Ireland (pronounced /ˈaɾlənd/ Éire) is the third largest island in Europe, and the twentieth-largest island in the world Extracts are usually in tablet or capsule form, and also in teabags and tinctures. A tablet is a mixture of active substances and Excipients usually in powder form pressed or compacted into a solid In the manufacture of pharmaceuticals encapsulation refers to a range of techniques used to enclose medicines in a relatively stable shell known as a capsule, allowing them In Medicine, a tincture is an Alcoholic Extract (eg of leaves or other plant material or Solution of a non- volatile substance There were now study proving that it helps to OCD sufferers. Obsessive-compulsive disorder (OCD is a Chronic Anxiety disorder most commonly characterized by obsessive Distressing Intrusive thoughts ^[8]

Clinical evidence

Clinical studies of St John's wort preparations have mainly focused on the efficacy of the herb in clinical depression. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression Several studies and meta-analyses have found it to be effective in the treatment of mild to moderate depression, with fewer side effects than many conventional antidepressants. In Statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses An antidepressant is a Psychiatric medication used for alleviating major depression or Dysthymia ('milder' depression Other studies, including a major National Institutes of Health (NIH) study that focused on participants with major depression, have shown no improvements. "NIH" redirects here For other meanings of NIH see NIH (disambiguation. ^[9]

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. In Statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses ^[10] 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 Review. The Cochrane Library is a collection of databases in medicine and other healthcare specialties provided by the Cochrane Collaboration and other organisations The updated review found that Hypericum preparations were significantly superior to placebo (rate ratio 2. 47; 95% confidence interval 1. In Statistics, a confidence interval (CI is an interval estimate of a Population parameter. 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). ^[11]

Another meta-analysis, with stricter inclusion criteria, found that Hypericum was more efficacious than placebo; and as efficacious as tricyclic antidepressants, with fewer adverse drug reactions. Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s This meta-analysis showed that the response rate for St John’s wort was significantly greater than that for placebo (73. Response rate (also known as completion rate or return rate) in survey research refers to the Ratio of number of people who answered the survey 2 versus 37. 9%, respectively, relative risk 1. In Statistics and mathematical Epidemiology, relative risk (RR is the risk of an event (or of developing a disease relative to exposure 48 and 95% CI 1. In Statistics, a confidence interval (CI is an interval estimate of a Population parameter. 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). ^[12]

There are some trials that show effectiveness of St. John's wort, beyond a placebo effect, on treating different types of depression. ^{[13][14][15][16][17][18][19]} 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. Dysthymia (pronounced /dɪsˈθaɪmiə/ is a Mood disorder that falls within the depression spectrum. It was concluded that St John's wort can be effective in the treatment of people with minor depression with a Hamilton Depression Scale for Depression (HAM-D) score of up to 17. The Hamilton Rating Scale for Depression ( HRSD) also known as the Hamilton Depression Rating Scale ( HDRS) or HAM-D, is a 21-question Multiple ^[20] The British Medical Journal has recommended that the results of the randomized controlled trials of St John's Wort should be interpreted with caution, as many did not use standardised preparations or homogenous populations, and doses of antidepressants varied. ^[10] A major review of the efficacy of St. John's Wort cautioned that the pharmaceutical quality of various preparations on the market may vary considerably. ^[11]

Evidence against efficacy for Major Depressive Disorder

A major study funded by the 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). "NIH" redirects here For other meanings of NIH see NIH (disambiguation. 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 Diagnostic and Statistical Manual of Mental Disorders' ( DSM) is published by the American Psychiatric Association The Hamilton Rating Scale for Depression ( HRSD) also known as the Hamilton Depression Rating Scale ( HDRS) or HAM-D, is a 21-question Multiple The Clinical Global Impression rating scales are commonly used measures of symptom severity treatment response and the efficacy of treatments in treatment studies of patients with mental disorders 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 statistically 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). ^[9] The authors of the study themselves, as well as several others pointed out the low assay sensitivity of this study, and how only limited conclusions can be drawn from its results. Assay sensitivity is a property of a Clinical trial defined as the ability of a trial to distinguish an effective treatment from a less effective or ineffective ^{[21] [22]}

Pharmacology

The exact mechanism by which St John's wort — and even conventional antidepressants — functions is unclear and subject to conjecture. The St John's wort mechanism is believed to involve inhibition of serotonin (5-HT) reuptake, much like the conventional selective serotonin reuptake inhibitor (SSRI) antidepressants. Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders ^[23] 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, flavonoids and tannins, may also be involved. Hyperforin is one of the principal constituents identified in St John's wort. Hypericin is a red-coloured Anthraquinone -derivative which is together with Hyperforin one of the principal active constituents of Hypericum ( The term flavonoid (or bioflavonoid refers to a class of Plant Secondary metabolites According to the IUPAC nomenclature they can be classified into Tannins are Astringent, bitter plant Polyphenols that either bind and Precipitate or shrink Proteins The astringency from the tannins is what ^[24][25][26]

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. Hyperforin is one of the principal constituents identified in St John's wort. Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Gamma-aminobutyric acid (GABA is the chief inhibitory Neurotransmitter in the Mammalian Central nervous system. Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its ^[25] On the other hand, a hyperforin free extract of St John's wort (Ze 117 - Remotiv) has been shown to still have significant antidepressive effects. ^[13][14]

Other medical uses

In addition to antidepressant, there are other medical uses for St John's wort:

It may also decrease alcohol intake. The constituent hyperforin, (found in the plant), appears to be responsible for decreasing alcohol consumption. Hyperforin is one of the principal constituents identified in St John's wort. ^[27]

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. An herbal tea, tisane, or ptisan is an Herbal Infusion made from anything other than the leaves of the Tea bush ( Camellia

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). Meticillin ( INN, BAN) or methicillin ( USAN) is a narrow spectrum Beta-lactam antibiotic of the Penicillin class Staphylococcus aureus (ˌstæfɨləˈkɒkəs ˈɔriəs literally "Golden Cluster Seed" and also known as golden staph) is the most common cause of ^[28]

Adverse effects

St John's wort is generally well tolerated, with an adverse effect profile similar to placebo. Placebo is a substance or procedure a patient accepts as medicine or therapy but which has no specific therapeutic activity ^[29] The most common adverse effects reported are gastrointestinal symptoms, dizziness, confusion, tiredness and sedation. ^[30]

St John's wort may rarely cause photosensitivity. Photodermatitis, or sometimes called by the nonscientific term sun poisoning, is a reaction of the Skin to UV rays of the Sun, or Photoallergy This can lead to visual sensitivity to light and to sunburns in situations that would not normally cause them. ^[29] Related to this, researchers at Fordham University, New York, showed in laboratory experiments that the drug reacts with light, both visible and ultraviolet, to produce free radicals, molecules that can damage the cells of the body. Fordham University is a private University in the United States, with three campuses located in and around New York City. In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell ^[31] These can react with vital proteins in the eye which, if damaged, precipitate out causing cataracts. Precipitation is the formation of a Solid in a Solution during a Chemical reaction. A cataract is a clouding that develops in the crystalline lens of the Eye or in its envelope varying in degree from slight to complete opacity

Some research shows that St John's wort may adversely affect fertility in both men and women. ^[32]

St John's wort has been known to instigate mania in bipolar patients and for these people it should be used with caution, just as with any anti-depressant. ^[33][34]

Caution is also recommended when discontinuing use.

Also, it is important to note that St John's Wort interacts with many drugs, so if a person is taking any other medications, they should talk with a doctor or pharmacist to see if it may interact.

Drug interactions

Pharmacokinetic interactions

St John's wort has been shown to cause multiple drug interactions mainly through induction of the cytochrome P450 enzyme CYP3A4, but also CYP2C9. Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity. Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism Cytochrome P450 2C9 (abbreviated CYP2C9) is an important Cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds 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. Hyperforin is one of the principal constituents identified in St John's wort.

Examples of drugs causing clinically-significant interactions with St John's wort

Class	Drugs
antiepileptics	carbamazepine, phenytoin
antiretrovirals	non-nucleoside reverse transcriptase inhibitors, protease inhibitors
benzodiazepines	alprazolam, midazolam
hormonal contraception	combined oral contraceptives
immunosuppressants	calcineurin inhibitors, ciclosporin, tacrolimus
others	digoxin, methadone, omeprazole, phenobarbitone, theophylline, warfarin, levodopa
Reference: Rossi, 2005

For a complete list, see CYP3A4#CYP3A4 ligands and CYP2C9#CYP2C9 Ligands. The anticonvulsants, also called antiepileptic drugs (abbreviated "AEDs" are a diverse group of pharmaceuticals used in the treatment of epileptic Carbamazepine ("CBZ" is an Anticonvulsant and mood stabilizing drug used primarily in the treatment of Epilepsy and Bipolar disorder Phenytoin sodium is a commonly used Antiepileptic. Phenytoin acts to dampen the unwanted runaway brain activity seen in seizure by reducing electrical conductance among brain Reverse transcriptase inhibitors (RTIs are a class of Antiretroviral drug used to treat HIV infection Tumors, and Cancer. The benzodiazepines (pronounced, often abbreviated to "benzos") are a class of Psychoactive drugs with varying Hypnotic Alprazolam, also known under the trade names Xanax and Niravam, is a short-acting drug of the Benzodiazepine class used to treat moderate Midazolam (marketed under brand names Dormicum, Flormidal, Versed, Hypnovel and Dormonid, pronounced mɪˈdæzəlæm Hormonal contraception refers to Birth control methods that act on the hormonal system Oral contraceptives come in a variety of formulations The main division is between Combined oral contraceptive pills containing both Estrogen and synthetic Progestogens An immunosuppressant is a substance that performs Immunosuppression of the Immune system. For a list of immunosuppressive drugs see the Transplant rejection page. Ciclosporin (ˌsaɪkləˈspɔrən cyclosporine ( USAN) or cyclosporin (former BAN) is an Immunosuppressant drug widely Tacrolimus (also FK-506 or Fujimycin) is an immunosuppressive drug whose main use is after allogenic Organ transplant to reduce the Digoxin ( INN) (dɨˈdʒɒksɨn also known as Digitalis, is a purified Cardiac glycoside extracted from the Foxglove plant Digitalis Methadone ( Dolophine Amidone Methadose Physeptone Heptadon and many others is a synthetic Opioid, used medically as an Analgesic, Antitussive Omeprazole ( INN) (oʊˈmɛprəzoʊl is a Proton pump inhibitor used in the treatment of Dyspepsia, peptic ulcer disease (PUD Gastroesophageal Phenobarbital ( INN) or phenobarbitone (former BAN) is a Barbiturate, first marketed as Luminal by Friedr Theophylline, also known as dimethylxanthine, is a Methylxanthine drug used in therapy for Respiratory diseases such as COPD or Asthma Warfarin (also known under the brand names Coumadin, Jantoven, Marevan, and Waran) is an Anticoagulant. Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism Cytochrome P450 2C9 (abbreviated CYP2C9) is an important Cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds For further updating on interactions and appropriate management, see 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 by up to 50%. ^[35]

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). Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use inadvertent interactions between drugs or the recreational Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. ^[36]

Drugs which may contribute to serotonin syndrome with St John's wort

Class	Drugs
antidepressants	MAOIs, TCAs, SSRIs, mirtazapine, venlafaxine
opioids	tramadol, pethidine
CNS stimulants	phentermine, diethylpropion, amphetamines, sibutramine
5-HT1 agonists	triptans
illicit drugs	methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), cocaine
others	selegiline, tryptophan, buspirone, lithium, linezolid, dextromethorphan, 5-HTP
Reference: Rossi, 2005

History

The first recorded use of Hypericum for medicinal purposes dates back to ancient Greece, and it has been used ever since. An antidepressant is a Psychiatric medication used for alleviating major depression or Dysthymia ('milder' depression Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Mirtazapine is an Antidepressant introduced by Organon International in 1994 used for the treatment of moderate to severe depression. Venlafaxine (Effexor Efexor is an Antidepressant of the Serotonin-norepinephrine reuptake inhibitor (SNRI class first introduced by Wyeth in 1993 An opioid is a chemical Substance that has a Morphine -like action in the body Tramadol ( INN) (ˈtræmədɒl is an atypical Opioid which is a centrally acting Analgesic, used for treating moderate to severe Pain. Pethidine ( INN) or meperidine ( USAN) (commonly referred to as Demerol but also referred to as isonipecaine lidol pethanol piridosal Algil Alodan Stimulant drugs are Drugs that temporarily increase alertness and awareness Phentermine, a contraction for " '''phen'''yl - '''ter'''tiary-butyl[[amine a' mine' ]]" is an Appetite suppressant of the Amphetamine Diethylcathinone (also called Diethylpropion and Amfepramone) is a Sympathomimetic Stimulant drug marketed as an appetite Amphetamine, and related drugs such as Methamphetamine are a group of drugs that act by increasing levels of Norepinephrine, Serotonin, and Dopamine Sibutramine (trade name Meridia in the US and Canada Reductil in Europe and most other countries usually as sibutramine hydrochloride monohydrate is an orally In the field of Neurochemistry, 5-HT receptors are receptors for the Neurotransmitter and peripheral signal mediator Serotonin, also Triptans are a family of Tryptamine based drugs used as Abortive medication in the treatment of Migraine and Cluster headaches They MDMA ( 34-methylenedioxy- N -methylamphetamine) most commonly known today by the street name Ecstasy (often abbreviated E, X, Cocaine ( benzoylmethyl ecgonine) is a Crystalline Tropane Alkaloid that is obtained from the leaves of the Coca plant Selegiline (l-deprenyl Eldepryl Zelapar or Anipryl Veterinary) is a drug used for the treatment of early-stage Parkinson's disease, Depression Tryptophan (abbreviated as Trp or W) is one of the 20 standard amino acids, as well as an Essential amino acid in the Human diet Buspirone (brand-names Ansial, Ansiced, Anxiron, Axoren, Bespar, BuSpar, Buspimen, Buspinol, Lithium in pharmacology refers to use of the Lithium Ion, Li+ as a drug Linezolid ( INN) (lɪˈnɛzəlɪd is a synthetic Antibiotic of the Oxazolidinone class used for the treatment of infections caused by multi-resistant Dextromethorphan ( DXM or DM) is an Antitussive (cough suppressant drug found in many over-the-counter cold and Cough medicines 5-Hydroxytryptophan or 5-HTP is a naturally-occurring Amino acid, a precursor to the Neurotransmitter Serotonin and an intermediate The term ancient Greece refers to the period of Greek history lasting from the Greek Dark Ages ca Hypericum was also used by Native Americans internally as an abortifacient and externally as an anti-inflammatory, astringent, and antiseptic. For indigenous peoples in the United States other than Hawaii and Alaska see also Native Americans in the United States. An abortifacient is a substance that induces Abortion. Abortifacients for Animals that have mated undesirably are known as Mismating shots Anti-inflammatory refers to the property of a substance or treatment that reduces Inflammation. An astringent (also spelled adstringent) substance is a chemical that tends to shrink or constrict Body tissues usually locally after Topical medicinal Antiseptics (from Greek αντί - anti, '"against" + σηπτικός - septikos, "putrefactive" are antimicrobial

Its use as a herbal tea has long been enjoyed. An herbal tea, tisane, or ptisan is an Herbal Infusion made from anything other than the leaves of the Tea bush ( Camellia

The flowers and stems of St John's wort have also been used to produce red and yellow dyes. A dye can generally be described as a Colored substance that has an affinity to the substrate to which it is being applied

References

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
• List of plants poisonous to equines

External links

• QuackWatch article on St John's wort Criticism of the use of St. This is a list of Plants which are Poisonous to Equines. Some may cause mild reactions such as Diarrhea, others can lead to serious problems including 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.

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