Premenstrual Syndrome: The Natural Approach

By Hwaa Irfan



Premenstrual tension, more commonly known as Premenstrual Syndrome (PMS), is known to be the bane of the lives of many busy women. It doesn’t have to be that way. Differing approaches can make naturally occuring processes in the body more tolerable if wetake the time to see what our bodies are telling us. Our bodies are not machines, but organic entities that require nutritional consideration and, at times of disease, actions that can bring our bodies back into balance.

PMS: More Than Just a Nuisance

PMS is known to be associated in some extreme cases with increased incidences of anti-social behavior, accidents, illnesses, and psychiatric crises. Drops in standards at school, forgetfulness and decreased punctuality are also known to occur. Aggressive behavior and inexplicable mood swings resulting from PMS can affect relations with family and friends. Temporary agoraphobia (fear of open or public places), panic attacks, phobias, a feeling of detachment and feelings of suspicion are also manifestations of extreme cases of pre-menstrual syndrome (Lockie & Geddes p.66, 67).

When looking at our lifestyles, we must include patterns of food consumption as possible contributory factors. Researchers have found that PMS patients consume 62% more refined carbohydrates, 275% more sugar, 79% more dairy products, 78% more sodium, 77% less manganese, 53% less iron and 52% less zinc than women who are free of symptoms (Lockie & Geddes p.6. The increased consumption of meat, poultry and their products that have been nurtured on hormones creates accummulative deposits within our bodies. Those hormones include the sex hormones progesterone, testosterone and estrogen. Introduced this way into our bodies they can lead to obesity, infertility, diabetes, dwarfism, gigantism, kidney disease, hypertension, early puberty, hypoglycemia, the masculinzation of females and cancer. They can also cause abortions, change the menstrual cycle and cause excessive breast and uterus tenderness (Colbin p.163,164).

One woman who visited nutritionist Annemarie Colbin complained of painful swelling of the breasts due to PMS. Annemarie recommended that the woman cease taking her daily quart of milk.

Patterns of food consumption must be taken into consideration

After a month there was a difference. After five months the soreness had stopped and only returned after the woman had eaten some cheese and ice cream. Annemarie Colbin recommends

that women with problems of the reproductive system should avoid all foodstuffs that relate to the reproductive system of animals or contains natural or artificial hormones i.e milk and milk products, eggs, and the meat of animals raised on estrogen (Colbin p.153, 283).

For those of us who might find the task more difficult, there are self-help approaches that can be made. As a step towards eliminating the causes, naturopaths recommend a high fiber diet, low fat, increased vegetable proteins, fruit and whole grains. They also recommend a diet high in calcium and iodine as that found in beans, leafy greens, alfalfa and kelp (Stein p.256, 257).

A Natural Remedy for an Age-Long Malady

A medicinal tree renowned of old for helping women through the menopause is the chaste tree also known as Vitex Agnus or in Arabic as bengenkusht, kef maryam or habb el-faqad (Manniche p.155). Recent studies have found it to be effective in PMS and even in reducing acne associated with PMS. The dark berries imitate the action of the female hormones estrogen and progesterone. It acts on the pituitary gland and balances the ovarian hormones by increasing the level of progesterone in relation to estrogen. Consequentially, this regulates the menstrual cycle thus alleviating PMS symptoms.

A recent German study found chaste tree to be more effective than Vitamin B6 supplements in PMS. This double-blind study involved 175 women who were followed over a period of 3 menstrual cycles. The women took either chaste tree together with a placebo, or Vitamin B6 supplements. When chaste tree was taken, milder symptoms of abdominal bloating, breast tenderness and irritability occurred. There were improvements in 77% of the women who took chaste tree and 61% of the women who took B6 supplements (New Straits p.1).

Chaste tree is known to reduce symptoms of premenstrual syndrome

In the 1987 trials of Exeter University and Gerard House (UK) led by statistician Susan Turner, 600 women who had a suitable range of symptoms were selected (Mills p.32). Utilizing the double-blind method, there were good results for 3 categories of PMS sufferers:-

a) PMT-H – fluid retention, breast tenderness, abdominal bloating, weight gain.

b) PMT-A – irritability, nervous tension, mood swings, anxiety.

c) PMT-D – depression, crying, confusion, forgetfulness and insomnia (Mills p.39).

In the German authorities’ listing of chaste tree (Bundesanzeiger Nummer 90, vomm 15,05,85) no contraindications are listed. However, under ‘Side-Effects’ chaste tree occasionally causes menstruation to start earlier after childbirth due to its action on the pituitary gland (Mills p.34).

An infusion can be taken by pouring a cup of boiling hot water on 1 teaspoon of the ripe berries. Leave to infuse for 10-15 minutes. Drink 3 times daily. It is also available as a tincture whereby 1-2 ml can be taken 3 times daily (Hoffman p.185). Health and well-being expert Alix Kirsta recommends more sleep and relaxation exercises for PMS sufferers. Wearing loose clothes also helps to allow the body to relax (Kirsta p.174).

Sources:

*

Colbin. Annemarie. “Food & Healing”. US. Ballantine Books. 1986.
*

Hoffman. David. “The Holistic Herbal”. Britain. Element Books. 1988.
*

Kirsta. Alix. “The Book of Stress Survival”. Britain. Unwin Paperbacks. 1988.
*

Lockie. Andrew & Geddes. Nicola. “The Women’s Guide to Homeopathy”. Britain. Hammish Hamilton. 1992.
*

Manniche. Lisa “An Ancient Egyptian Herbal” Britain. British Museum Publ. Ltd. 1989.
*

Mills. Simon. Woman Medicine: Vitex Agnus-Castus”. Britain. Amberwood Publishing Ltd. 1992.
*

Stein. Diane. “The Natural Remedy Book for Women”. US. Cassandra Press. 1992.
*

New Straits Times-Management Times. “Herbs Alleviate Symptoms of PMS”. 1-2. Asia WorldSources Inc. 1-2. Healthy News. Health World Online. 09/03/01.

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more info

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Beat PMT Cookbook

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Taking 1000mg of evening primose oil and st Johns wort
assist the body to re-balance.

but DONT st Johns wort if you want to have a baby its bad for that its it can cause damage to the sperm eggs

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St. John's wort - not take if trying for a baby

Adverse effects/toxicology. Side effects have included rash caused by photosensitivity, stomach upset, fatigue, sedation, dizziness, anxiety, and dry mouth. Some studies have indicated that St. John's wort may have adverse effects on sperm cells, possibly causing decreased fertility.8

8. David S. Tatro, ed. Drug Interaction Facts: Herbal Supplements and Food. Saint Louis, MO; Facts and Comparisons, A. Walters Kluwer Company; 2004. Also available online at:

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comparisons.com.

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High-dose Herbs Damage Sperm

St. John's wort and echinacea damaged sperm DNA and compromised sperm viability. Only the high concentration of St. John's wort was associated with a point mutation of the BRCA1 gene. Saw palmetto was the only herb that did not have a negative effect on penetration.


St. John's Wort Causes Cataracts
Sun trap - People using the herb St John's wort, a popular antidepressant, should take care if going out into the sunshine. Researchers from New York have found that a combination of St John's wort and bright light could lead to cataracts - New Scientist

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St. John's Wort

Hypericum perforatum

Principal Proposed Uses
• Mild to Moderate Depression
Other Proposed Uses
• Anxiety; Diabetic Neuropathy and Other Forms of Neuropathy ; Eczema (Topical Cream) ; Insomnia; Menopause; PMS; Seasonal Affective Disorder (SAD)
Probably Ineffective Uses
• Viral Infections

Page Navigation
What Is St. John's Wort Used for Today?
What Is the Scientific Evidence for St. John's Wort?
Dosage
Safety Issues
Transitioning from Medications to St. John's Wort
Interactions You Should Know About
References

http://www.swedish.org/110919.cfm


For the professional-level monograph, see also St. John's Wort.

St. John's wort is a common perennial herb of many branches and bright yellow flowers that grows wild in much of the world. Its name derives from the herb's tendency to flower around the feast of St. John. (A "wort" is simply a plant in Old English.) The species name perforatum derives from the watermarking of translucent dots that can be seen when the leaf is held up to the sun.

St. John's wort has a long history of use in treating emotional disorders. During the Middle Ages, St. John's wort was popular for "casting out demons," conceivably an archaic description of curing mental illness. In the 1800s, the herb was classified as a "nervine," or a treatment for "nervous disorders." It began to be considered a treatment for depression in the early 1900s, and when pharmaceutical antidepressants were invented, German researchers began to look for similar properties in St. John's wort.
What Is St. John's Wort Used for Today?

Today, St. John's wort is a widely used treatment for depression in Germany, other parts of Europe, and the United States. The evidence-base for its use approaches that of many modern prescription drugs at the time of their first approval. Indeed, this herb is a prescription antidepressant in Germany, covered by the national health-care system, and is prescribed more frequently for depression than any synthetic drug.

Most studies of St. John's wort have evaluated individuals with major depression of mild to moderate intensity. This contradictory-sounding language indicates that the level of depression is more severe than simply feeling "blue." However, it is not as severe as the most intense forms of depression. Typical symptoms include depressed mood, lack of energy, sleep problems, anxiety, appetite disturbance, difficulty concentrating, and poor stress tolerance. Irritability can also be a sign of depression.

Taken as a whole, research suggests that St. John's wort is more effective than placebo and approximately as effective as standard drugs. Furthermore, St. John's wort appears to cause fewer side effects than many antidepressants. However, the herb does present one significant safety risk: it interacts harmfully with a great many standard medications (see Safety Issues for details).

Warning: St. John's wort should never be relied on for the treatment of severe depression. If you or a loved one feels suicidal, unable to cope with daily life, paralyzed by anxiety, incapable of getting out of bed, unable to sleep, or uninterested in eating, see a physician at once. Drug therapy may save your life.

Besides depression, St. John’s wort has also been tried for many other conditions in which prescription antidepressants are thought useful, such as attention deficit disorder, anxiety, insomnia, 15menopausal symptoms, 20PMS, 19 and seasonal affective disorder (SAD). 98,99 However, there is no direct evidence as yet that it offers any benefit for these conditions.

Standard antidepressants are also often used for diabetic neuropathy, and other forms of neuropathy (nerve pain). However, a small double-blind, placebo-controlled trial failed to find St. John's wort effective for this purpose. 16

St. John’s wort contains, among other ingredients, the substances hypericin and hyperforin. Early reports suggested that St. John's wort or synthetic hypericin might be useful against viruses such as HIV, but these haven't panned out. 17 However, there is some evidence hyperforin may be able to fight certain bacteria, including some that are resistant to antibiotics. 18 Note: this evidence is far too preliminary to count St. John's wort as an effective antibiotic.

Based on weak evidence that hypericin might have anti-inflammatory properties, St. John’s wort cream has been tried as a treatment for eczema, with some promising results. 100
What Is the Scientific Evidence for St. John's Wort?
Depression

The results of numerous studies suggest St. John's wort is effective for mild to moderate depression.

There have been two main kinds of studies: those that compared St. John's wort to placebo, and others that compared it to prescription antidepressants.

St. John's Wort Versus Placebo

Studies of St. John's wort (and other antidepressants) use a set of questions called the Hamilton Depression Index (HAM-D). This scale rates the extent of depression, with higher numbers indicating more serious symptoms.

Double-blind, placebo-controlled trials involving a total of more than a thousand participants with major depression of mild to moderate severity have generally found that use of St. John's wort can significantly reduce HAM-D scores as compared to placebo. 21–28,89

For example, in a 6-week trial, 375 individuals with average 17-item HAM-D scores of about 22 (indicating major depression of moderate severity) were given either St. John's wort or placebo. 89 Individuals taking St. John's wort showed significantly greater improvement than those taking placebo.

Two double-blind, placebo-controlled trials evaluating individuals with a similar level of depression have failed to find St. John’s wort more effective than placebo. 27,85,89 However, two studies cannot overturn a body of positive research. Keep in mind that 35% of double-blind studies involving pharmaceutical antidepressants have also failed to find the active agent significantly more effective than placebo. 85 As if to illustrate this, in the more recent of the two trials in which St. John’s wort failed to prove effective, the drug sertraline (Zoloft) also failed to prove effective. The reason for these negative outcomes is not that Zoloft (or Prozac, or any other drug) does not work. Rather, statistical effects can easily hide the benefits of a drug, especially in a condition like depression where there is as a high placebo effect and no really precise method of measuring symptoms.

Thus, unless a whole series of studies find St. John’s wort ineffective, especially trials in which a comparison drug treatment does prove effective, St. John’s wort should still be regarded as probably effective for major depression of mild to moderate severity.

St. John's Wort Versus Medications

Several studies have found that St. John’s wort is equally as effective as standard antidepressants, but causes fewer side effects.

The largest of these trials was a 6-week, double-blind trial of 240 people with mild to moderate depression that compared St. John's wort (250 mg twice daily of a 4–7:1 alcohol extract) to fluoxetine (Prozac) at the standard dose of 20 mg daily. 31 The results showed that St. John's wort at least as effective as Prozac, and caused fewer and less severe side effects.

Four other double-blind trials enrolling a total of more than 300 people have compared St. John’s wort to either fluoxetine (Prozac) or sertraline (Zoloft). 32,33,90,91 In all of these studies, the herb proved as effective as the drug, and caused fewer side effects.

St. John’s wort has also been compared to older antidepressants.

An 8-week study of 263 individuals with moderate depression compared the effectiveness of a slightly high dose of St. John's wort (350 mg 3 times daily of an extract standardized to contain 2 to 3 % hyperforin) against placebo and the somewhat outdated, but nonetheless effective, antidepressant imipramine. 34 The results showed that imipramine and St. John's wort were equally effective, and both were more effective than placebo.

However, according to a double-blind study of 209 people, St. John's wort, even in double the usual dose, is not as effective as imipramine for major depression of high severity. 35

Ten other trials enrolling individuals with major depression of mild to moderate severity have compared St. John's wort against old-fashioned but tried-and-true antidepressants including imipramine, maprotiline, and amitriptyline, and found equivalent benefits. 36–38 However, these studies used excessively low doses of the standard drug, and therefore proved little.

How Does St. John’s Wort Work?

Like pharmaceutical antidepressants, St. John's wort is thought to raise levels of neurotransmitters in the brain, such as serotonin, norepinephrine, and dopamine. 6,7

The active ingredient of St. John’s wort is not known. Extracts of St. John’s wort are most often standardized to the substance hypericin, which has led to the widespread misconception that hypericin is the active ingredient. However, there is no evidence that hypericin itself is an antidepressant. Another ingredient of St. John's wort named hyperforin has shown considerable promise as the most important ingredient.

Hyperforin was first identified as a constituent of Hypericum perforatum in 1971 by Russian researchers, but it was incorrectly believed to be too unstable to play a major role in the herb's action. 1 However, subsequent evidence corrected this view. It now appears that standard St. John's wort extract contains about 1 to 6% hyperforin. 2 Evidence from animal and human studies suggests that it is the hyperforin in St. John’s wort that raises the levels of neurotransmitters. 8–10 Nonetheless, there may be other active ingredients in St. John's wort also at work. 11,12 In fact, two double-blind trials using a form of St. John's wort with low hyperforin content found it effective. 13,14 The bottom line remains that more research is necessary to discover just how St. John’s wort acts against depression.
Polyneuropathy

A double-blind, placebo-controlled trial of 54 people with diabetic neuropathy or other forms of neuropathy (pain, numbness and/or tingling caused by injury to nerves) did not find St. John's wort effective for this purpose. 40
Dosage

The standard dosage of St. John's wort is 300 mg 3 times a day of an extract standardized to contain 0.3% hypericin. A few new products on the market are standardized to hyperforin content (usually 2 to 3%) instead of hypericin. These are taken at the same dosage. Some people take 500 mg twice a day, or 600 mg in the morning and 300 mg in the evening.

Yet another form of St. John's wort has also passed double-blind studies. This form contains little hyperforin, and is taken at a dose of 250 mg twice daily. 41,42

If the herb bothers your stomach, take it with food.

Remember that the full effect takes 4 weeks to develop. Don't give up too soon!
Safety Issues

St. John's wort taken alone usually does not cause immediate side effects. In a study designed to look for side effects, 3,250 people took St. John's wort for 4 weeks. 43 Overall, about 2.4% reported problems. The most common complaints were mild stomach discomfort (0.6%), allergic reactions—primarily rash—(0.5%), tiredness (0.4%), and restlessness (0.3%). Another study followed 313 individuals treated with St. John's wort for 1 year. 44 The results showed a similarly low incidence of adverse effects.

In the extensive German experience with St. John's wort as a treatment for depression, there have been no published reports of serious adverse consequences from taking the herb alone. 45 Animal studies involving enormous doses of St. John's wort extracts for 26 weeks have not shown any serious effects. 46

However, there are a number of potential safety risks with St. John's wort that should be considered. These are outlined in the following sections.
Photosensitivity

Cows and sheep grazing on St. John's wort have sometimes developed severe and even fatal sensitivity to the sun. In one study, highly sun-sensitive people were given twice the normal dose of the herb. 47 The results showed a mild but measurable increase in reaction to ultraviolet radiation. Another trial found that a one-time dose of St. John’s wort containing 2 or 6 times the normal daily dose did not cause an increased tendency to burn; nor did seven days of treatment at the normal dose. 83 However, there is a case report of severe and unexpected burning in an individual who used St. John's wort and then received ultraviolet therapy for psoriasis. 48 In addition, two individuals using topical St. John's wort experienced severe reactions to sun exposure. 84

The morals of the story are as follows: if you are especially sensitive to the sun, don't exceed the recommended dose of St. John's wort, and continue to take your usual precautions against burning; if you are receiving UV treatment, do not use St. John’s wort at all; and if you apply St. John’s wort to your skin, keep that part of your body away from the sun.

In addition, you might get into problems if you combine St. John's wort with other medications that cause increased sun sensitivity, such as sulfa drugs and the anti-inflammatory medication Feldene (piroxicam). The medications Prilosec (omeprazole) and Prevacid (lansoprazole) may also increase the tendency of St. John's wort to cause photosensitivity. 49

Finally, a report suggests that regular use of St. John's wort might also increase the risk of sun-induced cataracts. 50 While this is preliminary information, it may make sense to wear sunglasses when outdoors if you are taking this herb on a long-term basis.
Drug Interactions

Herbal experts have warned for some time that combining St. John's wort with drugs in the Prozac family (SSRIs) might raise serotonin too much and cause a number of serious problems. Recently, case reports of such events have begun to trickle in. 51,52,53 This is a potentially serious risk. Do not combine St. John's wort with prescription antidepressants except on the specific advice of a physician. Since some antidepressants, such as Prozac, linger in the blood for quite some time, you also need to exercise caution when switching from a drug to St. John's wort.

Antimigraine drugs in the triptan family (such as sumatriptan, or Imitrex) and the pain-killing drug tramadol also raise serotonin levels and might interact similarly with St. John's wort. 54,55

Perhaps the biggest concern with St. John's wort is the possibility that it may decrease the effectiveness of various medications, including protease inhibitors (for HIV infection), cyclosporine (for organ transplants), digoxin (for heart disease), statin drugs (used for high cholesterol) warfarin (a blood thinner), chemotherapy drugs, oral contraceptives, tricyclic antidepressants, olanzapine or clozapine (for schizophrenia), and theophylline (for asthma). 56–67,80,82,87,88,92,93,95 Furthermore, if you are taking St. John's wort and one of these medications at the same time and then stop taking the herb, blood levels of the drug may rise. This rise in drug level could be dangerous in certain circumstances.

These interactions could lead to catastrophic consequences. Indeed, St. John's wort appears to have caused several cases of heart, kidney, and liver transplant rejection by interfering with the action of cyclosporine. Also, many people with HIV take St. John's wort in the false belief that the herb will fight AIDS. The unintended result may be to reduce the potency of standard anti-HIV drugs.

In addition, the herb appears to decrease the effectiveness of oral contraceptives and by doing so is thought to have caused unwanted pregnancies. 68,88

Finally, one report suggests that use of St. John’s wort may interact with anesthetic drugs. 101

The bottom line: We recommend that people taking any oral or injected medication that is critical to their health or wellbeing should entirely avoid using St. John's wort until more is known. On general principles, we also advise avoid using the herb prior to undergoing general anesthesia.
Safety in Special Circumstances

One animal study found no ill effects on the offspring of pregnant mice. 69 However, these findings alone are not sufficient to establish St. John's wort as safe for use during pregnancy. Furthermore, the St. John's wort constituent hypericin can accumulate in the nucleus of cells and directly bind to DNA. 70 For this reason, pregnant or nursing women should avoid St. John's wort. Furthermore, safety for use by young children or people with severe liver or kidney disease has not been established.

Like other antidepressants, case reports suggest that St. John's wort can cause episodes of mania in individuals with bipolar disorder (manic-depressive disease). 71,72

There is also one report of St. John's wort causing temporary psychosis in a person with Alzheimer's disease. 79
Other Concerns

Certain foods contain a substance named tyramine. These foods include aged cheeses, aged or cured meat, sauerkraut, soy sauce, other soy condiments, beer (especially beer on tap) and wine. Drugs in the MAO inhibitor family interact adversely with tyramine, causing severe side effects such as high blood pressure, rapid heart rate and delirium. One case report suggests that St. John’s might present this risk as well. 96 However, other studies suggest that normal doses of St. John’s should not cause MAO-like effects. 4,5,97 Until this issue is sorted out, we recommend that individuals taking St. John’s wort avoid tyramine-containing foods. Since MAO inhibitors react adversely with stimulant drugs such as Ritalin, ephedrine (found in the herb ephedra) and caffeine, we also recommend that you avoid combining St. John’s wort with them.

One small study suggests that high doses of St. John's wort might slightly impair mental function. 73

One case report associates use of St. John's wort with hair loss. 74 The authors note that standard antidepressants may also cause hair loss at times.

One study raised questions about possible antifertility effects of St. John's wort. When high concentrations of St. John's wort were placed in a test tube with hamster sperm and ova, the sperm were damaged and less able to penetrate the ova. 75 However, since it is unlikely that this much St. John's wort can actually come in contact with sperm and ova when they are in the body rather than in a test tube, these results may not be meaningful in real life.
Transitioning from Medications to St. John's Wort

If you are taking a prescription drug for mild to moderate depression, switching to St. John's wort may be a reasonable idea if you would prefer taking an herb. To avoid overlapping treatments, the safest approach is to stop taking the drug and allow it to wash out of your system before starting St. John's wort. Consult with your doctor on how much time is necessary.

However, if you are taking medication for severe depression, switching over to St. John's wort is not a good idea. The herb probably won't work well enough, and you may sink into a dangerous depression.
Interactions You Should Know About

If you are taking

* Antidepressant drugs, including MAO inhibitors, SSRIs, and tricyclics; or possibly the drugs tramadol or sumatriptan (Imitrex): Do not take St. John's wort at the same time. Actually, you need to let the medication flush out of your system for a while (perhaps weeks, depending on the drug) before you start the herb.
* Digoxin, cyclosporine, protease inhibitors (for HIV infection), oral contraceptives, tricyclic antidepressants, Coumadin (warfarin), statin drugs (used for high cholesterol), theophylline, chemotherapy drugs, newer antipsychotic medications (such as olanzapine and clozapine) or, indeed, any critical medication:St. John's wort might cause the drug to be less effective. Furthermore, if you are already taking St. John's wort and your physician adjusts your medication dosage to achieve proper blood levels, suddenly stopping St. John's wort could cause the level of the drug in your body to rebound to dangerously high levels.
* Medications that cause sun sensitivity such as sulfa drugs and the anti-inflammatory medication Feldene (piroxicam), as well as Prilosec (omeprazole) or Prevacid (lansoprazole): Keep in mind that St. John's wort might have an additive effect.
* Stimulant drugs or herbs such as Ritalin, caffeine, or ephedrine ( ephedra): it is possible that St. John’s wort might interact adversely with them.

References

1. Erdelmeier CAJ. Hyperforin, possibly the major non-nitrogenous secondary metabolite of Hypericum perforatum L. Pharmacopsychiatry. 1998;31(suppl 1):2–6.

2. Schulz V. Hyperforin-Werte keinesfalls nur "Spuren." Dtsch Apoth Ztg. 1998;138:65. Cited by: Chatterjee S, Noldner M, Koch E, et al. Antidepressant activity of Hypericum perforatum and hyperforin: the neglected possibility. Pharmacopsychiatry. 1998;31(suppl 1):7–15.

3. Suzuki O, Katsumata Y, Oya M, et al. Inhibition of monoamine oxidase by hypericin. Planta Med. 1984;50:272–274.

4. Bladt S, Wagner H. Inhibition of MAO by fractions and constituents of hypericum extract. J Geriatr Psychiatr Neurol. 1994;7(suppl 1):S57–S59.

5. Thiede HM, Walper A. Inhibition of MAO and COMT by hypericum extracts and hypericin. J Geriatr Psychiatr Neurol. 1994;7(suppl 1):S54–S56.

6. Muller WE, Rossol R. Effects of hypericum extract on the expression of serotonin receptors . J Geriatr Psychiatry Neurol. 1994;7(suppl 1):S63–S64.

7. Muller WE, Kasper S, Volz HP, et al. Hypericum extract (LI160) as an herbal antidepressant. Pharmacopsychiatry. 1997;30(suppl 2):71–134.

8. Muller WE, Singer A, Wonnemann M, et al. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry. 1998;31(suppl 1):16–21.

9. Ghattacharya SK, Chakrabareti A, Chatterjee SS. Activity profiles of two hyperforin-containing hypericum extracts in behavioural models. Pharmacopsychiatry, 1998;31(suppl):22–29.

10. Laakmann G, Schle C, Baghai T, et al. St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry. 1998;31(suppl):54–59.

11. Dimpfel W, Schober F, Mannel M. Effects of a methanolic extract and a hyperforin-enriched CO2 extract of St. John's wort ( Hypericum perforatum) on intracerebral field potentials in the freely moving rat (Tele-Stereo-EEG). Pharmacopsychiatry. 1998;31(suppl 1):30–35.

12. Butterweck V, Jurgenliemk G, Nahrstedt A, et al. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta Med. 2000;66:3–6.

13. Schrader E. Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol. 2000;15:61–68.

14. Schrader E, Meier B, Brattstrom A. Hypericum treatment of mild-moderate depression in a placebo-controlled study: a prospective, double-blind, randomized, placebo-controlled, multicentre study. Hum Psychopharmacol. 1998;13:163–169.

15. Schulz H, Jobert M. The influence of hypericum extract on the sleep EEG in older volunteers [in German; English abstract]. Nervenheilkunde. 1993;12:323–327.

16. Sindrup SH, Madsen C, Bach FW, et al. St. John's wort has no effect on pain in polyneuropathy. Pain. 2001;91:361–365.

17. Gulick R, McAuliffe V, Holden-Wiltse J, et al. Phase I studies of hypericin, the active compound in St. John's wort, as an antiretroviral agent in HIV-infected adults. Ann Intern Med. 1999;130:510–514.

18. Schempp CM, Pelz K, Wittmer A, et al. Antibacterial activity of hyperforin from St John's wort, against multiresistant Staphylococcus aureus and gram-positive bacteria. Lancet. 1999;353:2129.

19. Stevinson C, Ernst E. A pilot study of Hypericum perforatum for the treatment of premenstrual syndrome. BJOG. 2000;107:870–876.

20. Grube B, Walper A, Wheatley D. St. John's Wort extract: efficacy for menopausal symptoms of psychological origin. Adv Ther. 1999;16:177–186.

21. Hansgen KD, Vesper J, Ploch M. Multicenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160. J Geriatr Psychiatry Neurol. 1994;7(suppl 1):S15–S18.

22. Laakmann G, Schle C, Baghai T, et al. St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry. 1998;31(suppl):54–59.

23. Schrader E, Meier B, Brattstrom A. Hypericum treatment of mild-moderate depression in a placebo-controlled study. A prospective, double-blind, randomized, placebo-controlled, multicentre study. Hum Psychopharmacol. 1998;13:163–169.

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