St. John’s Wort

What is St. John’s Wort?

St John’s wort or latin. Hypericum perforatum is a flowering plant in the family Hypericaceae. The common name “St John’s wort” is commonly used to refer any species of the genus Hypericum. Thus, Hypericum perforatum is sometimes called St John’s wort or perforate St John’s wort in order to better differentiate it. This plant with yellow flowers has been used in traditional medicine since ancient Greeks time.

The name St. John’s wort probably refers to John the Baptist, as the plant blossoms around late June, the days of the feast of St. John the Baptist. It is sold as an herbal supplement that doesn’t need any prescription and it can be bought at a health food store. It is available in the form of teas, tablets, capsules, topical preparations and liquid extracts.

What is St. John’s Wort used for?

This herb has been used for thousands years because of medical properties with antidepressant activity and potent anti-inflammatory activity because it works as an arachidonate 5-lipoxygenase and COX-1 inhibitor. St John’s wort can be also used to treat nervousness, difficulty sleeping, insomnia, kidney and lung ailments and infections.

People also use St John’s Wort as a dietary supplement for other disorders, including menopausal symptoms, attention-deficit hyperactivity disorder and obsessive-compulsive disorder. Topically it can be used for wound healing. Although St. John’s wort has been used for centuries for mental issues and is widely prescribed for depression treatment in Europe, this herbal supplement can have serious interactions with other drugs and side effects.

Additionally, current evidence is that St. John’s wort has not conclusive effectiveness in depression treatment. It is also important to know that in the U.S., FDA has not approved St John’s Wort as an OTC or prescription medication for depression.

St. John’s wort has also been studied for conditions including: quitting smoking, irritable bowel syndrome, ADHD and there are no evidences that it is helpful. For others, such as premenstrual syndrome, menopausal symptoms, and obsessive-compulsive disorder the evidence of effctiveness is questionable.

St. John’s Wort composition

Hypericin, pseudohypericin, and hyperforin are most dominant active ingredients in St John’s Wort and may be measured in plasma and thus make adequate dosage. These three active ingredients have elimination half-lives within a range of 15–60 hours in humans. None of them can be detected in urine samples.

The plant contains the following ingredients:

• Flavonoids (e.g.  rutin, hyperoside,  isoquercetin, quercitrin, quercetin,  biapigenin, amentoflavone, astilbin, miquelianin, myricetin, kaempferol, luteolin)
• Phenolic acids (e.g. caffeic acid, chlorogenic acid, p-coumaric acid, ferulic acid, p-hydroxybenzoic acid, vanillic acid)
• Naphthodianthrones (e.g. hypericin, pseudohypericin, protopseudohypericin, protohypericin)
• Phloroglucinols (e.g. hyperforin, adhyperforin)
• Tannins (unspecified, proanthocyanidins)
• Volatile oils (e.g. nonane, 2-methyldecane, 2-methyloctane, undecane, α-terpineol, α-pinene, β-pinene,  geraniol, limonene, myrcene, caryophyllene, humulene)
• Saturated fatty acids(e.g. isovaleric acid (3-methylbutanoic acid), palmitic acid, myristic acid, stearic acid)
• Alkanols (e.g. 1-tetracosanol, 1-hexacosanol)
• Vitamins (e.g.carotenoids, choline, nicotinamide, nicotinic acid)
• Miscellaneous others (e.g.pectin,  hexadecane, β-sitosterol, triacontane, kielcorin, norathyriol)

What are different Brand names for St. John’s Wort?

St. John’s Wort is available under different Brand names such as: Amber, Barbe de Saint-Jean, Chasse-diable, Amber Touch-and-Heal, Demon Chaser, Hardhay, Herbe à la Brûlure, Fuga Daemonum, Goatweed,  Herbe Aux Mille Vertus, Herbe Aux Piqûres, Herbe à Mille Trous, Herbe Aux Fées,  Herbe de Saint Éloi, Herbe de la Saint-Jean, Herbe du Charpentier, Herbe Percée, Hierba de San Juan, Hypereikon, Hyperici Herba, Hypericum perforatum, Klamath Weed, Millepertuis, Millepertuis Perforé, Rosin Rose, Saynt Johannes Wort, SJW, Tipton Weed.

St. John’s Wort oil

Oil can be produced from St. John’s wort. Some people uses this this oil by mouth for indigestion problems while others apply this oil to their skin to treat inflammation, bruises and scrapes and muscle pain, psoriasis, first degree burns, tooth pulling, wounds, bug bites, hemorrhoids, nerve pain, and to treat a disease that causes the skin to lose color. However applying St. John’s wort directly to the skin may cause side effects such as serious sensitivity to sunlight.

How St. John’s Wort works in the body?

St. John’s wort, like other herbs, is made of different chemical molecules with various pharmacologic, thus it may be used for various therapeutic purposes.  Phloroglucinol compounds such as Hyperforin and Adhyperforin are agonists of TRPC6 receptors that induce inhibition of noncompetitive reuptake of monoamines such as norepinephrine, dopamine, serotonin, GABA, and glutamate when they activate ion channel.

Probably most dominant active ingredient of St. John’s wort – hyperforin is also an inhibitor of so called PTGS1, arachidonate 5-lipoxygenase, gene SLCO1B1 and an inducer of Multidrug resistance-associated protein 2 – cMOAT. Hyperforin contains anti-inflammatory, anti-angiogenic, antimicrobial and neurotrophic properties.

It has been showed that hyperforin is antagonist of NMDA receptors, which is a type of glutamate receptor. Furthermore, St John’s wort is able to downregulate the β1 adrenoceptor and upregulate postsynaptic 5-HT1A and 5-HT2A serotonins receptors. Many other compounds can also play a significant role in St John’s wort’s antidepressant effects.

These compounds may include: flavonoids (quercetin), oligomeric procyanidines, hypericin, and pseudohypericin.

St. John’s Wort and depression

St. John’s wort may be helpful for some types of depression. Some studies showed that these plant antidepressive effects are similar to treatment with regular prescription antidepressants; however the evidence is not definitive.

Larger and more relevant studies are needed toconfirm that. Although it is commonly prescribed for depression treatment in Europe, Food and Drug Administration didn’t approve its use as an OTCr or prescription medicine for depression in the United States.

Study results on the of St. John’s wort effectiveness for depression are different. Here are some findings:

• A systematic review of 29 studies from 2009 revealed that St. John’s wort may be more efficient than a placebo and as effective as standard prescription antidepressants for the treatment of major depression disorders of mild to moderate severity. St. John’s wort also showed to have fewer side effects than standard antidepressants.
• Studies conducted in German-speaking countries where St. John’s wort has a long tradition of use and prescriptions by medical professionals have been showed more positive results than studies conducted in other countries, including the United States.
• Two studies, sponsored by the National Institute of Mental Health and NCCIH did not show positive results. A large study from 2002 showed that St. John’s wort was no more effective than placebo in treating major depression disorder of moderate severity. The study from 2011 has been found that neither St. John’s wort nor a standard antidepressant pharmacologic treatment decreased symptoms of minor depression better than a placebo.

St. John’s Wort placebo effect for depression

The placebo effect describes health improvements that are not related with known and active therapeutic effect. A recent analysis of the 2002 study on major depression treatment with St John’s Wort showed that the participants’ beliefs about whether they were taking a St. John’s wort or placebo influenced their depression more than the therapy they are actually taking.

It has been shown that even the way clinician talks to patients may lead to a positive response that is unrelated to the treatment. To confirm the usefulness of any intervention, more rigorous studies are needed in order to compare the product or practice being tested with comparable but inactive products or practices.

St. John’s Wort for menopausal symptoms

There is some evidence suggesting that some precise combinations of St. John’s wort and black cohosh (Remifemin) can be benefitial for the improvement of menopausal symptoms such as hot flashes. But, the effects of St. John’s wort individual on menopausal symptoms are unreliable. However, researchers suggest that St. John’s wort might reduce hot flashes.

St. John’s Wort for PMS

St. John’s wort benefits for the PMS treatment are questionable. Some early research suggests that St. John’s wort might help reduce PMS symptoms, including coordination, sleeping problems, confusion, headache, fatigue, crying, food cravings and swelling, by even as much as 50% in some women. However, other findings indicate that taking St. John’s wort does not reduce anxiety or other PMS symptoms.

St. John’s Wort for smoking cessation

It has been found that specific St. John’s wort extract called LI-160 if taken 1-2 times a day starting one week before and continuing for 3 months after quitting smoking does not improve long-term quit rates.

St. John’s Wort use after angioplasty

Recent studies showed that using St. John’s wort 3 times a day for 2 weeks after angioplasty improves outcomes of the procedure in patients who are also administrating blood thinning medications. It is suggested that St. John’s wort might help anticoagulants to work better in crtain patients.

St. John’s Wort for Attention deficit-hyperactivity disorder (ADHD)

There are some findings suggesting that taking St. John’s wort at daily basis during 4 weeks can improve attention and activity in adolescents with ADHD. But other studies show that taking a St. John’s wort extract during a period of 8 weeks does not improve ADHD symptoms in children ages 6-17 years.

St. John’s Wort for Anxiety

It has been shown that St. John’s wort alone or in combination with valerian may be beneficial for anxiety disorder. Also, taking Sedariston Concentrate capsules that contains fixed combination of valerian root and St. John’s Wort reduces anxiety more than the medication diazepam.

However, taking St. John’s wort daily does not seem to improve social phobia or social anxiety. There are also conflicting proofs about St. John’s wort effectiveness for opsesive-compulsive disorders.

St. John’s Wort for wound healing

Applying ointment with St. John’s wort 3 times a day for 16 days seems to improve wound healing and reduce scar formation after a Cesarean section.

St. John’s Wort for migraine headaches

It has been found that taking a specific St. John’s wort product called Perforan, three times a day reduces severity of migraine pain but does not reduce the frequency of migraine attacks.

St. John’s Wort for Hepatitis C virus (HCV) infection

Taking St. John’s wort by mouth does not seem to be effective for treating adults with hepatitis C virus infection.

St. John’s Wort for Irritable bowel syndrome (IBS)

It has been showed that taking a specific St. John’s wort extract such as: St. John’s Wort Extract Extra Strength twice a day is not effective for reducing symptoms of Irritable bowel syndrome

Can St. John’s Wort kill HIV virus?

Absolutely not! There are no studies that can prove even small benefits. Don’t use St. John’s wort for this condition.

St. John’s Wort for Herpes

There are some findings suggesting that using a specific combination of St. John’s wort and copper sulfate pentahydrate might help reduce herpes symptoms, including burning, stinging and pain, in patients with cold sores or genital herpes.

St. John’s Wort for Brain tumors (glioma)

Early research suggest that taking hypericin, a substance from St. John’s wort, by mouth for up to 3 months may reduce the size of a tumor and improve the survival rate in people with brain tumors.

St. John’s Wort dosage

It has to be known that St. John’s Wort medications are not FDA approved for many indications. However there are dosage recommendations that should be followed for safely treatment of next disorders:

Depression, Mild-moderate:

Hypericin 0.3% standardized extract

• 300 mg orally 3 times a day or
• 1200 mg orally per day

Hypericin 0.2% standardized extract: 250 mg 2 times a day

Hyperforin 5% standardized extract: 300 mg orally 3 times a day

Crude: 2-4 g orally per day

Obsessive-compulsive Disorder:

Hypericin 0.3% standardized extract (XR): 450 mg orally 2 times a day

Premenstrual Syndrome:

Hypericin 0.3% standardized extract: 300 mg orally once a day

How much long can I take St. John’s Wort supplements?

St. John’s Wort supplements should not be taken for more than 8 weeks. Patients should also avoid abrupt discontinuation due to withdrawal effects.

Warnings and preacautions during St. John’s wort use:

• IMPORTANT WARNING: St. John’s wort must not be used with certain antidepressants, as their interaction can lead to a potentially life-threatening condition called serotonin syndrome due to increase of serotonin levels. St. John’s wort can also reduce the effectiveness of many prescription medicines.
• John’s wort is not approved therapy for depression. Never use St. John’s wort to substitute conventional therapy given by your health care provider. Ineffectively treated depression may become more severe and in some cases, may lead to suicide. Consult your doctor if you or someone you know may be depressed.
• Patients should know that dietary supplements including St. John’s wort can cause medical issues if not used properly or if used in high doses, and some may interact with medications you take. Your health care provider can counsel you about this.
• John’s wort has not been properly tested in pregnant women, nursing mothers, or children. Little safety data on St. John’s wort for pregnant women or children is available, so it is very important to talk with health experts if you are pregnant or nursing or if you want to give a supplement to a child.
• Tell your doctor about any complementary health approaches you use.
• John’s wort may cause some of following side effects: allergic reactions, fatigue and restlessness with long-term use, increased blood pressure, increased sensitivity to the sun — especially if you are fair-skinned and taking large doses, stomach upsets
• It has been shown that St. John’s wort may lower the effectiveness of several drugs, including birth control pills, heart disease medications and drugs used to prevent organ transplant rejections
• If you are taking St. John’s wort for the treatment of depression and your symptoms do not improve after 4 to 6 weeks of regular use, contact your doctor. Contact your doctor as soon as possible if your symptoms become worse of if your depression becomes severe.

St John’s Wort side effects

St John’s Wort is normally well tolerated, with side effect profile similar to placebo. However in some rare cases it may cause following side effects:

• Agitation
• Anxiety
• Dizziness
• Dry mouth
• Fatigue
• GI discomfort
• Headache
• Hypomania
• Insomnia
• Irritability
• Menstrual irregularities
• Paresthesias
• Photosensitivity
• Restlessness
• Skin rash

In very rare cases St. John’s wort may cause photosensitivity reactions. This can lead to visual issues to light and to sunburns in situations that would not normally cause them. Also, it has been shown that St John’s wort is related with provoking psychosis in people who have schizophrenia.

St John’s Wort interactions

St. John’s wort is known to cause serious interactions if it is taken with other drugs.

• Combining St. John’s wort and certain antidepressants such as SSRIs, MAOIs and tricyclic ant depressives can lead to a potentially life-threatening condition called serotonin syndrome. Symptoms of this syndrome may include following: tremor, diarrhea, confusion, muscle stiffness, reduced body temperature, and even death.
• St .John’s wort also decreases the levels of many drugs by speeding up its metabolism as it upregulates the liver enzyme called CYP3A4 cytochrome of theP450 system in the  St. John’s wort can weaken the effects of many different prescription medicines, such as:
  • Antidepressants
  • Cyclosporine, which prevents the body from rejecting transplanted organs
  • Birth control pills
  • Digoxin
  • Some HIV drugs including indinavir
  • Some cancer medications including irinotecan
  • Warfarin and other blood thinners

St. John’s Wort overdose and poisoning in humans and animals

If it is taken in large doses St. John’s wort can be very poisonous. Signs of poisoning are general restlessness and skin irritations. Restlessness is often described by pawing of the ground, head rubbing, headshaking and occasional panting, confusion, and depression.

Mania and agitation may also happen. Animals poisoned with St John’s Wort usually seek shade and have reduced appetite. Hypersensitivity to water has also been noted, and convulsions may also occur

Severe skin has been also described, with reddening of non-pigmented and unprotected areas, subsequently leading to itch and rubbing and followed by further inflammation, scab formation and exudation.

Sheep poisoned with this plant have been observed to have and wool falling, face swelling and dermatitis. Lactating animals may stop to produce milk or have reduced milk production while pregnant animals may abort. Horses may show signs of anorexia, depression dilated pupils, and injected conjunctiva.

St. John’s Wort during pregnancy

St. John’s Wort shouldn’t be used during pregnancy. It has been showed that this plant may cause increased uterine muscle contractions in laboratory animals leading to abortions. One small study showed higher incidence of miscarriage in pregnant woman where the mothers were taking St. John’s Wort compared to the treatment with antidepressants or no antidepressant, the rates between these three groups were not significantly different.

There are no studies observing the exposure to St. John’s Wort and withdrawal symptoms or effects on the newborn behavior, growth and development. Any possible related risks are unknown. It is known that tannic acid present in St. John’s Wort may prevent iron absorption which is an important mineral during pregnancy and for fetus development.

A small study that observed 49 pregnancies with at least first trimester exposure to St. John’s Wort did not find an increase in birth defects compared to women taking prescription antidepressant medication. Larger studies are needed to confirm that.

In specific situations where a pregnant woman is significantly depressed St. John’s Wort is never recommendable due to lack of studies, so healthcare provider may prescribe some other drug well studied antidepressant.

St. John’s Wort during breastfeeding

One small study on5 breastfeeding woman of full-term older infants (10-22 weeks) showed that the amount of St. John’s Wort that infants received through the breast milk was very small. The mothers reported no side effects in their infants.

Another study conducted on 33 women who use St. John’s Wort and breastfed, showed a higher incidence of side effects such are colic and drowsiness when compared to a group of infants whose mothers had depression but were not administrating St John’s Wort. The infants did not need medical treatment.

As a long-acting drug, it is expected from St. John’s Wort that after ingestion by the infant would remain in the body for a long time. More studies are needed to confirm St. John’s Wort safety during breastfeeding.

St. John’s Wort and surgery

Use of anesthesia in patients who have used St. John’s wort for more than 6 months may lead to serious heart complications during surgery. St. John’s wort should be discontinued for at least 2 weeks before a scheduled surgery.

Can patients with Bipolar disorder use St. John’s Wort?

Patients with bipolar disorder should avoid St. John’s Wort, because this herb can bring on mania and can also speed up the cycling between depression and mania.

Can I take St. John’s Wort and Xanax together?

St. John’s wort can increase how fast the body metabolizes alprazolam which is the active ingredient of Xanax. Taking St. John’s wort together with Xanax might decrease the effectiveness of Xanax. The proposed mechanism is induction of CYP450 3A4 mediated intestinal first-pass and hepatic metabolism by constituents of St. John’s wort.

Patients who uses Xanax during long-term might experience withdrawal symptoms such as blurred vision, loss of appetite, trouble concentrating, diarrhea, numbness or tingling, muscle twitching or increased sensations. However, effects of the interaction can be very variable due to differences in composition of St. John’s wort mixture and deviation from labeled claims of many herbal products.

Can I take St. John’s Wort and Birth control pills together?

These two medicines should not be taken together. St. John’s wort might increase the metabolism of estrogen found in birth pills decreasing the effectiveness of birth control pills.

The exact mechanism of interaction remains unknown but it may involve reduced absorption of birth pill as well as accelerated elimination of the hormones due to intestinal induction of P-glycoprotein drug efflux transporter and intestinal and hepatic CYP450 3A4 metabolism by compounds found in St. John’s wort.

There have been also reports of menstrual breakthrough bleeding in patients receiving long-term oral contraceptives in combination with this herb, and cases of unplanned pregnancies. If you take birth control pills along with St. John’s wort it is recommended to use an additional form of birth control such as a condom.

Can I take St. John’s Wort and Digoxin together?

St. John’s wort might reduce the absorbtion of Digoxin thus decreasing the effects of digoxin.

Can I take St. John’s Wort and Ketamine together?

St. John’s wort may induce the metabolism of ketamine and decrease its anesthetic effectiveness.

Can I take St. John’s Wort and Warfarin together?

St. John’s wort might increase metabolism and decrease the effectiveness of warfarin taken at the same time. Decreasing the effectiveness of warfarin, St. John’s Wort might increase the risk of clotting.. The dose of your warfarin (Coumadin) might need to be changed.

Can I take St. John’s Wort together with antidepressants (Prozac, Zoloft, Paxil, etc.)?

Using antidepressants such as Zoloft, Prozac, Paxil, or any SSRI, TCA or MAOI, or any other drug that impacts serotonin levels together with St. John’s wort can increase the risk of causing a rare but very serious condition called the serotonin syndrome, which may provoke symptoms such as: confusion, seizure, hallucination, fever excessive sweating, extreme changes in blood pressure, increased heart rate, shivering or shaking, tremor, incoordination, blurred vision, muscle spasm or stiffness, stomach cramp, nausea, vomiting, and diarrhea.

Severe cases may result in coma and even death. The proposed mechanism is hyperstimulation of brainstem 5-HT1A and 2A receptors.

Does St. John’s Wort interact with food? What food should I have to avoid during St. John’s Wort use?

Patients, who are taking St. John’s wort, must not eat or drink certain foods and beverages that contain high amounts of tyramine. Eating these foods while taking St. John’s wort can increase your blood pressure to dangerous levels.

This interaction may cause life threatening symptoms such as sudden and severe headacheblurred vision, confusion, problems with speech or balance, nausea, seizure (convulsions), vomiting, chest pain and sudden numbness or weakness.

Foods that are high in tyramine may include: aged or fermented meats, air dried meats, sausage or salami, spoiled or improperly stored beef,  aged cheeses, including blue, brick, brie, cheddar, parmesan, romano, and swiss, sauerkraut, pickled herring, poultry, fish, or liver, red wine, beer from a tap, beer that has not been pasteurize, OTC products or cough and cold medicines that contain tyramine, soy beans, soy sauce, miso soup, tofu,  bean curd, fava beans, or yeast extracts (such as Marmite). Caffeine intake should be limited as well.

Can I take St. John’s Wort and Alcohol together?

Patients should avoid or limit alcohol use while being treated with St. John’s wort. Alcohol can increase the nervous system side effects such as dizziness, drowsiness, and difficulty concentrating. Some people, especially elderly may also experience impairment in thinking and judgment. Talk to your doctor or pharmacist if you have any questions or concerns.

Can I take St. John’s Wort together with cyclosporine?

Coadministration of cyclosporin and St. John’s wort may reduce the blood levels and pharmacologic effects of cyclosporine. The mechanism involves reduced absorption as well as accelerated elimination due to induction of intestinal P-glycoprotein and hepatic/intestinal CYP450 3A4 isoenzymes by compounds of St. John’s wort.

Using these medications together can make cyclosporine less effective increasing the risk of organ rejection associated with low cyclosporine levels.

Can I take St. John’s Wort together with indinavir or other anti-HIV drugs?

Using these drugs together may cause indinavir to be less effective. St. John’s wort may reduce the plasma concentrations of certain antiretroviral agents such as nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors and CCR5 coreceptor antagonists. The mechanism is induction of CYP450 3A4 metabolism by St. John’s wort compounds.

Can I take St. John’s Wort together with Irinotecan?

Preparations containing St. John’s wort may reduce the blood levels of irinotecan, making the medication less effective in treating cancer. The mechanism is induction of CYP450 3A4, the enzyme that is partially responsible for the metabolism of irinotecan.

Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications.

Can I take St. John’s Wort together with Benadryl?

Using Benadryl together with St. John’s wort may increase side effects such as dizziness, confusion, drowsiness and difficulty concentrating. Some people, especially the elderly, may also experience impairment in thinking, judgment, and motor coordination.

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