e-tarded

do a search in this forum it has been covered before plenty of times. i am not trying to be rude, but no one uses the search function ever. might as well use it if we have it. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

no it doesn't. there are like 12 other threads in this forum on the same exact subject. if you do a search you can find out more information too. but to answer your question it doesnt interfere. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

If you go ahead and decide to use Illustrator or whoever does. Remember to convert all fonts to outlines. If you need any help or have any questions, feel free to email me or to pm me. I would be glad to help. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

Well you are going to need a layout program, like Quark Express, Pagemaker or Adobe Indesign. You can ever use Microsoft Publisher. For the graphics part you need Photoshop ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

From Ecstasy.org Ecstasy use by a diabetic I am currently 29 years old. I am also a well controlled and healthy type 1 (insulin dependent, shot-taking) diabetic since age thirteen. When I was about 23-24 I was heavyly into the local club scene and at the time at least, Ecstasy happened to be popular, high quality and plentiful. Dealers where seemingly everywhere as well as the people on it and it wasn't hard to tell they where all enjoying themselves a lot. I had never taken a "hard drug" in my life, not cocaine, speed, LSD or anything other than alcohol or pot, mainly out of fear of addiction as well as my paranoia of seeing things that just aren't there. But I started to consider taking E after hearing about it's fascinating effects. I spent a good week or two talking to those who were experienced in the matter and discussed in great detail the onset, apogee and come-down times as well as the after effects, possible side effects and psychological and physical ramifications in all their possibilities. After all of that I deemed that as long as I was careful about my diabetes when tripping everything would be fine. I started making careful preparations for the big night. My first concern would be that when on any drug such as E, which can alter one's perception of one's own bodily state, that I might not be able to feel a hypoglycemic (low blood sugar) episode coming on. That was possibly dangerous since these usually require the drinking of a 12 ounce soda about 8 minutes after you first notice it. Let it go any further and passing out is a real risk. Usually the feeling of nervousness or disorientation particular to hypoglycemia is enough to let me know I need that soda, but on E, I thought, that feeling may have been masked. So my first and virtually only concern was the avoidance of hypoglycemia. Once again, I prepared for this eventuality in advance. When "zero night" came, everything was set to my satisfaction. My car was parked not too far from the club where I was to take it. In the car was a stock of 3 12 oz. soda cans, my portable glucose meter and plenty of strips to use with it. I intended testing every half hour during the hardest part of the trip and then every 45 minutes as I came down. I knew most of the people at the club by name and any of them would help me if I should have requested. I also made it well known to them that I was a first timer with E. I had a few closer friends there to help with the diabetic details. I told them about all of my concerns and preparation plans, I made sure they where staying straight that night so they'd be able to assist if I needed it and most importantly I showed them how to use my blood meter and even where to find it's miniature instruction card. The meter was basically foolproof anyway, but just to make sure, I had them do everything from pricking my finger to assessing the results so there was no doubt whatsoever. That also put my mind to rest. I wanted to enjoy this trip and not be paranoid while on the journey. My friends were instructed, in the event of my impaired judgment, to get me a soda and make me drink it immediately if my blood sugar fell to 70 or less. They where also instructed to escort me to the car for a test and soda every half hour or whenever I felt like it. Their support made this possible. Even earlier that night I took less than the usual amount of insulin after dinner so my blood sugar would be more stable and even a bit higher afterwards, but nowhere near dangerous levels. I bought a hit from a known dealer on Friday night and waited until Saturday when I went out to get everyone's reaction about the batch he'd been selling and it's safety. No one had a bad trip so it was a go. I took only half a tab which is all I strongly recommend for first time users. After taking it I set my watch to count down to the 45 minute onset time. After much anticipation and even fear, it kicked in and was a great trip.... hard rolling, muscle tension, ecstasy, openness and an energy coursing through my body that was pure zen. It was better than I could possibly have imagined. I walked a lot which I knew was going to lower my blood sugar so the testing came in handy all right. Naturally the sugar did go down to about 70 but I was at all times coherent enough to test my own blood (I was supervised anyway) and to judge when I needed that soda. Eating some food afterwards would have been ideal but since E killed my appetite so badly I only consumed the soda. I lusted for water and I didn't have an appetite for the soda since it wasn't going to quench my thirst but it wasn't too hard to force it down in a minute or two. I recovered just fine in the usual 3 post consuming minutes, no difference there. As the testing and the trip progressed I noticed no wild fluctuations in blood sugar and nothing that wasn't commensurate with my activity level and other factors normally influencing blood sugar in a diabetic. At the end of the trip, or at least when I felt okay about stopping the half hourly testing, my blood sugar was an ideal 150. I took a small shot of insulin and went to get something to eat since I'd been left ravenous by the experience. I believe that tripping for those who have diabetes isn't inherently dangerous. But all trips, for those with diabetes, have to include the usual common sense measures (moderation, plenty of water, etc.) as well as fail-safe measures for getting your blood sugar tested and responded to. With experience I learned that I could test by myself but I always let people who knew I was diabetic and who would be around know that I was X'ing when I did it. http://www.ecstasy.org/experiences/trip85.html ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

wow thats really a tough one... :-/ hmmmm... I know I covered this a while ago, but I have no idea if I have the article anymore. I will check around to see if I have it. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

What do diazepam tablets do? DIAZEPAM (Valium®) is a benzodiazepine. Benzodiazepines belong to a group of medicines that slow down the central nervous system. Diazepam relieves anxiety and nervousness. It also can help patients cope with alcohol withdrawal, relax muscles, and treat certain types of seizures (convulsions). Federal law prohibits the transfer of diazepam to any person other than the patient for whom it was prescribed. Do not share this medicine with anyone else. Generic diazepam tablets are available. What should my health care professional know before I take diazepam? They need to know if you have any of these conditions: •an alcohol or drug abuse problem •depression •glaucoma •kidney or liver disease •lung disease or breathing difficulties •myasthenia gravis •Parkinson's disease •psychosis •shock, or coma •shortness of breath •snoring •suicidal thoughts •an unusual or allergic reaction to diazepam, other benzodiazepines, foods, dyes, or preservatives •pregnant or trying to get pregnant •breast-feeding How should I take this medicine? Take diazepam tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. If diazepam upsets your stomach, take it with food or milk. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your prescriber's advice. Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed. Elderly patients over 65 years old may have a stronger reaction to this medicine and need smaller doses. What if I miss a dose? If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses. What other medicines can interact with diazepam? •alcohol •barbiturate medicines for inducing sleep or treating seizures (convulsions) •chloroquine •cimetidine •digoxin •disulfiram •erythromycin •female hormones, including contraceptive or birth control pills •fluvoxamine •isoniazid •some medicines for hay fever and other allergies •medicines for mental problems and psychotic disturbances •some medicines for pain •omeprazole •rifampin •valproic acid Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines. What side effects may I notice from taking diazepam? Side effects that you should report to your prescriber or health care professional as soon as possible: •confusion •depression •lightheadedness or fainting spells •mood changes, excitability or aggressive behavior •movement difficulty, staggering or jerky movements •muscle cramps •problems passing urine •restlessness •skin rash •speech difficulty •tremors •weakness or tiredness Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome): •difficulty sleeping, nightmares •dizziness, drowsiness, clumsiness, or unsteadiness; a "hangover" effect •headache •nausea, vomiting What do I need to watch for while I take diazepam? Visit your prescriber or health care professional for regular checks on your progress. Your body can become dependent on diazepam, ask your prescriber or health care professional if you still need to take it. However, if you have been taking diazepam regularly for some time, do not suddenly stop taking it. You must gradually reduce the dose or you may get severe side effects. Ask your prescriber or health care professional for advice. Even after you stop taking diazepam it can still affect your body for several days. You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how diazepam affects you. To reduce the risk of dizzy and fainting spells, do not stand or sit up quickly, especially if you are an older patient. Alcohol may increase dizziness and drowsiness. Avoid alcoholic drinks. Do not treat yourself for coughs, colds or allergies without asking your prescriber or health care professional for advice. Some ingredients can increase possible side effects. If you are going to have surgery, tell your prescriber or health care professional that you are taking diazepam. Where can I keep my medicine? Keep out of the reach of children in a container that small children cannot open. Store at room temperature between 15 and 30 degreesC (59 and 86 degreesF). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

drugs are bad mmmmmmmmmmmmmkay ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

bump ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

Anyone here happen to work for Time Out New York the magazine? I have a question regarding employment there. Thanks ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

Nice post Not that I do drugs any longer, but I don't have a problem with people who do. Like you said everyone just have fun ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

Usual Suspects Bad Company Tech Itch and Decoder ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

it takes the body approximiately 8 hours to convert 5-HTP to seratonin. So taking it now really wouldn't do that much. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

mdma has a very bitter discernible taste, at least from experience. I have heard people though say they have gotten great pills that tasted nothing like regular pills. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

on one hand we have Stacker a stimulant on the other hand we have Ketamine a tranquilizer. any questions ? The question is why would you want to take them together.. They do completely opposite things. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By.... [This message has been edited by e-tarded (edited 01-26-2001).]

Well you have 5-HTP (hydroxy-tryptophan) also wanna supplement that with Niacin. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

try this site http://www.eyecandie.bizland.com/index2.htm but really the best way to learn is by watching people or even going up to them and asking them to show you. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

St. John's wort (SJW) is a perennial herb native to Europe, North Africa, and western Asia. It has been introduced and naturalized in parts of Africa, Asia, Australia, and the Americas, and is found growing wild in neglected fields, dry pastures, rangelands, and along country roads (Bombardelli and Morazzoni, 1995; Leung and Foster, 1996; Snow, 1996; Upton, 1997; Wichtl and Bisset, 1994). In European medicine, SJW was traditionally obtained from Eastern European countries, where it is still wild collected (BHP, 1996; Braun et al., 1997; Wichtl and Bisset, 1994). It is cultivated in at least four provinces in Germany (Lange and Schippmann, 1997). The SJW used in Indian Ayurvedic medicine is distributed in the temperate western Himalayas, Kashmir, and Simla (Karnick, 1994; Nadkarni, 1976). SJW was initially brought to the northeastern United States by European colonists (Pickering, 1879; Upton, 1997). It is harvested from naturalized plants in the Pacific Northwest and eastern states (Upton, 1997). Since the mid-1990s, in order to meet new demands on supply, it has been quickly brought into large-scale cultivation in Europe, North and South America, Australia, and China. Many of SJW's therapeutic applications (except antiviral use), including its uses as a vulnerary, diuretic, and treatment for neuralgic conditions, stem from traditional Greek medicine, originally documented by ancient Greek medical herbalists Hippocrates (ca. 460–377 B.C.E.), Theophrastus (ca. 372–287 B.C.E.), Dioscorides (first century C.E.), and Galen (ca. 130–200 C.E.) (Bombardelli and Morazzoni, 1995; Hobbs, 1990; Leung and Foster, 1996; Upton, 1997). Since the time of Swiss physician Paracelsus (ca. 1493–1541 C.E.) it has been used to treat psychiatric disorders. At that time it was described as "arnica for the nerves" (Reuter, 1998). The aerial flowering parts of SJW have been used in traditional European medicine for centuries to treat neuralgia, anxiety, neurosis, and depression (Rasmussen, 1998). The traditional way to take SJW was as herbal tea, an aqueous extract whose single dose corresponded to 2–3 g of dried crude drug (Schulz et al., 1997). In the nineteenth and twentieth centuries, American Eclectic physicians prescribed SJW to treat hysteria and nervous affections with depression. It was prescribed externally to treat wounds, bruises, sprains, and much more (Ellingwood, 1983; Felter and Lloyd, 1983; Felter, 1985; King, 1866; Snow, 1996; Upton, 1997). Today, St. John's wort is official in the national pharmacopeias of Czechoslovakia, France, Poland, Romania, and Russia (Bruneton, 1995; Hobbs, 1989; Newall et al., 1996; Ph.Fr.X, 1990; Reynolds, 1993; Upton, 1997; USSR X, 1973). In Germany, SJW is listed in the German Drug Codex, approved as a medicine in the Commission E monographs, and licensed as a standard medicinal tea infusion (BAnz, 1998; Braun et al., 1997; DAC, 1991; Meyer-Buchtela, 1999; Schilcher, 1997; Wichtl and Bisset, 1994). It is used in psychiatric drugs in forms including dampoule (Hyperforat®), coated tablet (LI 160, Jarsin®, Lichtwer Pharma, Berlin), juice (Kneipp® Johanniskraut Pflanzensaft N), tea (Kneipp® Johanniskraut-Tee), and tincture (Psychotonin®M). It is used in some urological preparations affecting micturition (e.g., Inconturina®) (Kneipp®, 1996; Schilcher, 1997; Wichtl and Bisset, 1994). In German pediatric medicine, SJW aqueous infusions, alcoholic fluidextracts, and some proprietary products (such as Sedariston®, a combination of SJW and valerian (Valeriana officinalis) extracts) are used to treat depressive states in young people. For example, SJW is a component of a sedative tea for children, composed of 30% lemon balm leaf (Mellissa officinalis), 30% lavender flower (Lavandula officinalis), 30% passion flower herb (Passiflora spp.), and 10% SJW herb (Schilcher, 1997). In the United States it is used in a wide range of dietary supplements in forms including alcoholic tincture, aqueous infusion (oral), oil infusion (topical), and dry standardized extract in capsules and tablets (Leung and Foster, 1996; Upton, 1997). In 1998, the United States Pharmacopeia Drug Information division issued a therapeutic monograph and consumer information bulletin stating that the USP Advisory Panels do not recommend or support the use of SJW because they believe that there have not been enough quality studies to prove that it is effective. However, USP noted that research indicated the safety of SJW (USP-DI, 1998). The USP also published an identification monograph that included guidelines for assessing the identity and purity of raw material in bulk or powder form (USP, 1999a). Since 1979, there have been about 30 controlled trials with Hypericum extracts, involving thousands of patients with mild to moderate depressive disorders. Most studies lasted 28 to 42 days with daily dosages of 900 mg of an extract standardized to 0.3% hypericin (Jarsin®, LI 160, Lichtwer Pharma, Berlin). Up to 1997, there have been at least 15 controlled studies on a methanolic extract of SJW (LI 160) and 12 controlled studies on four additional preparations made from ethanolic extracts of SJW (Schulz et al., 1998). They have confirmed the antidepressant action of SJW extracts in humans (Bombardelli and Morazzoni, 1995; Linde et al., 1996; Reuter, 1998; Upton, 1997). These studies on SJW do not meet the criteria for conventional antidepressant drugs according to the regulatory guidelines of the European Union, thereby keeping SJW from being accepted for treatment for major depression (De Smet and Nolen, 1996). However, some of these same deficiencies relate to studies on conventional antidepressants when they are first marketed (Cott, 1999). Studies that compare treatment with SJW to treatment with a synthetic antidepressant have not lasted longer than six weeks and have been compared using about one-half the usual dose of the antidepressant (75 mg imipramine instead of 150 mg). In addition, they have not been conducted with severely depressed patients. Yet SJW has been shown to be safe, with very few side effects, compared with synthetic antidepressants: out of 3,250 patients, only allergic reactions (0.5%), gastrointestinal upset (0.6%), and fatigue (0.4%) were observed (De Smet and Nolen, 1996). Evidence of the antidepressant activity of SJW extracts can be found in reviews by Bombardelli and Morazzoni (1995), Linde et al. (1996), and Upton (1997). No significant modern human studies investigating SJW's other therapeutic uses have been found (e.g., orally for dyspeptic complaints and topically for burns, lesions, wounds, and myalgia). The constituents and mechanism of action responsible for the antidepressant properties of SJW have been investigated, with various authors citing different mechanisms (Bombardelli and Morazzoni, 1995; Rasmussen, 1998; Reuter, 1995, 1998). However, a recent randomized, double-blind, placebo-controlled, multicenter study on 147 male and female patients with mild to moderate depression indicated that hyperforin may be the primary active ingredient, or at least it plays a key role in the antidepressant activity. Patients received 300 mg of either a placebo, a SJW extract standardized to 0.5% hyperforin (WS 5573, W. Schwabe, Germany), or a SJW extract standardized to 5% hyperforin (WS 5572, Schwabe), three times daily for 42 days. While there was a reduction in depression scores in both the 0.5% hyperforin group and the placebo group, results were statistically significant for improvement of depressive symptoms only in the patients receiving the extract with 5% hyperforin (Laakmann et al., 1998a, 1998b). Of particular interest is the finding that patients with severe depression (n=56) experienced greater reduction of symptoms than mild to moderately depressed patients receiving the same dosage (although there is more room for improvement in severely depressed patients). The authors of this study concluded that the antidepressant activity of SJW is due to its hyperforin content. Other experimental studies have also shown the relevance of hyperforin (Chatterjee et al., 1998; Bhattacharya et al., 1998). However, additional animal and human research is being conducted to clarify the importance of hyperforin, since most of the studies on St. John's wort were conducted on preparations standardized to hypericin, not hyperforin, content. Nevertheless, a representative of the leading manufacturer of the most clinically tested hypericin-based SJW extract (i.e., LI 160 from Lichtwer Pharma) has written that this product showed hyperforin levels of 1% to 6% upon analysis; new studies by Lichtwer on LI 160 will be carried out on an extract standardized to hyperforin values of approximately 4% (Schulz, 1998). Although additional research is warranted, the modern therapeutic application of SJW for mild to moderate depression is supported by its history of use in traditional medicine, in vitro studies (Cott, 1997; Wonnemann et al., 1999), in vivo experiments in animals (Butterweck et al., 1999; Okpanyi and Weischer, 1987), pharmacodynamic studies in humans (Kugler et al., 1990; Schulz and Jobert, 1993), pharmacokinetic studies in humans (Staffeldt et al., 1993; Weiser, 1991), human clinical studies (Hänsgen et al., 1994; Hübner et al., 1994; Cott, 1997; Fugh-Berman and Cott, 1999), meta-analyses (Linde et al., 1996) and extensive phytochemical investigations (Bombardelli and Morazzoni, 1995; Brantner et al., 1994). A major three-year, multicenter clinical study on the antidepressant effect of SJW is being carried out in the United States under the auspices of the National Institutes of Health. This is the first clinical study to test SJW directly against a modern selective serotonin reuptake inhibitor (SSRI) (sertraline, Zoloft®) and placebo. The trial consists of 330 patients (110 in each arm--SJW, sertraline, placebo) and the duration of treatment will last six months, the longest trial on SJW to date. Patients are required to test a minimum of 20 points on the Hamilton Depression Scale, thus being classed as moderately to severely depressed. A small study has investigated the possible use of SJW for seasonal affective disorder (SAD), a condition of depressive mood associated with winter months and lack of sunlight (Kasper, 1997). In an open study, 22 patients diagnosed with SAD were given SJW extract (300 mg three times daily) with additional bright light or the same dose of SJW in dim light conditions. As determined by a standard method for measuring depression symptoms (Hamilton Depression Scale), subjects in both groups experienced a significant reduction in depression score, there being no difference in the bright and dim light groups. Therefore, no conclusion for the effectiveness of SJW in SAD can be drawn from the results of this study. Pharmacopeial grade SJW consists of the dried flowering tops or aerial parts of Hypericum perforatum L., harvested shortly before or during the flowering period. It must contain not less than 12% water soluble extractive. Botanical identity must be confirmed by thin-layer chromatography (TLC), macrocopic and microscopic examinations, and organoleptic (sensory) evaluation (BHP, 1996). The German Drug Codex additionally required not less than 0.4% dianthrones of the hypericin group, calculated as hypericin (DAC, 1986; Wichtl and Bisset, 1994). The German Standard License monograph requires the material to conform with the German Drug Codex requirements (Braun et al., 1997). However, the German Federal Institute for Drugs and Medical Devices (BfArM) declared that hypericin would no longer be used as a required marker compound for the chemical standardization of St. John's wort (Bühler, 1995). The United States Pharmacopeia requires not less than 0.2% of hypericin and pseudohypericin combined and not less than 3.0% of hyperforin (USP, 1999b). The ESCOP monograph requires the material to conform with either the French Pharmacopoeia or the German Drug Codex (ESCOP, 1997). Description St. John's wort consists of the dried, aboveground parts of H. perforatum L. [Fam. Hypericaceae], gathered during flowering season, and their preparations in effective dosage. Chemistry and Pharmacology St. John's wort herb contains 6.5–15% catechin-type tannins and condensed-type proanthocyanidins (catechin, epicatechin, leucocyanidin); 2–5% flavonoids, mostly hyperoside (0.5–2%), rutin (0.3–1.6%), quercitrin (0.3%), isoquercitrin (0.3%), quercetin, and kaempferol; biflavonoids (approximately 0.26% biapigenin); phloroglucinol derivatives (up to 4% hyperforin); phenolic acids (caffeic, chlorogenic, ferulic); 0.05–1.0% volatile oils, mainly higher n-alkanes; 0.05–0.15% naphthodianthrones (hypericin and pseudohypericin); sterols (b-sitosterol); vitamins C and A; xanthones (up to 10 ppm); and choline (Bruneton, 1995; ESCOP, 1997; Leung and Foster, 1996; Newall et al., 1996; Wichtl and Bisset, 1994). The Commission E reported that a mild antidepressant action of the herb and its preparations has been observed and reported by many physicians. Although the Commission E categorized St. John's wort as an MAO inhibitor, this was based on in vitro research and not conducted in animal systems. Subsequent research has indicated either no or very slight MAO activity in St. John's wort or its preparations. The Commission E recognized the anti-inflammatory action of topical oily Hypericum preparations. The British Herbal Pharmacopoeia reported antidepressant action (BHP, 1996). In numerous controlled double-blind and open studies using hydroalcoholic SJW preparations, a significant improvement of mood, and loss of interest and activity and other depressive syndrome symptoms, such as sleep, concentration, and somatic complaints, has been reported (ESCOP, 1997). Uses In December 1984, the Commission E approved the internal use of St. John's wort for psychovegetative (psychoautonomic) disturbances, depressive moods, anxiety, and nervous unrest. Oily Hypericum preparations are approved for dyspeptic complaints. External use of oily preparations of St. John's wort is approved for treatment and post-therapy of acute and contused injuries, myalgia, and first-degree burns. ESCOP indicates its use for mild to moderate depressive states, restlessness, anxiety, and irritability (ESCOP, 1997). The German Standard License for St. John's wort tea lists it for nervous excitement and sleep disturbances (Wichtl and Bisset, 1994). With the exception of its antiviral use, other modern applications date back two thousand years (Hobbs, 1990). Since the 1984 monograph was based on general clinical use and only one clinical study (out of more than 27 that had been published up to 1997) had been published at that time, the Commission was relatively accurate in its evaluation of the therapeutic effects of SJW. However, given that most the recent research has focused on antidepressant activity of SJW, it is reasonable to conclude that this use should be the only primary use, when administered in proper form and dosage (Schulz et al., 1998). SJW may benefit the other uses (psychovegetative disturbances, anxiety, and nervous unrest) only within the framework of its general antidepressant activity (Schulz et al., 1998). Contraindications None known. Side Effects Commission E noted that photosensitization is possible, especially in fair-skinned individuals. However, animal and human research has indicated that photosensitization is not likely to occur at the recommended dosage levels. Based on experimental studies (animal and human), it would take approximately 30 to 50 times the recommended daily dose of 900 mg of the standardized extract to produce severe phototoxic effects in humans (Schulz et al., 1998). Use During Pregnancy and Lactation No restrictions known (McGuffin et al., 1997). Interactions with Other Drugs Commission E reported that none were known (in 1984). ESCOP also noted that none were reported (ESCOP, 1997). Dosage and Administration The original Commission E monograph (1984) noted the following dosage: "Unless otherwise prescribed: 2–4 g per day of chopped or powdered herb for internal use, or 0.2–1 mg of total hypericin in other forms of preparation application. Liquid and semi-solid preparations for external use. Preparations made with fatty oils for external and internal use." Although the original Commission E monograph specified minimum levels of hypericin, this is no longer required on the label of German products (Ahuis, 1998). In Germany, the current required dosage is 300 mg, three times daily of a hydroalcoholic St. John's wort extract. The registration for infusions (tea) of St. John's wort has recently been withdrawn due to a lack of evidence of efficacy (BfArM, 1998). Based on the available research, the approved effective equivalent preparations are as follows: Internal: Fluidextract 1:1 (g/ml): 2 ml, twice daily. Native dry extract 5–7:1: 300 mg, three times daily. External: Oily macerate (Oleum hyperici): macerate fresh flowering tops in olive oil or wheat-germ oil for several weeks, stirring often; strain through a cloth and press pulp; for direct application to affected areas. References Ahuis, F. 1998. Neues über Johanniskraut [News on St. John's Wort]. Deutsche Apotheker Zeitung 138:1783–1785. BAnz. See Bundesanzeiger. BfArM. 1998. Meeting of BfArM, Johanniskraut, No. 113. BPI [Federal Manufacturers Association]. 151. Bhattacharya, S.K., A. Chakrabarti, S.S. Chatterjee. 1998. Activity profiles of two hyperforin-containing Hypericum extracts in behavioral models. Pharmacopsychiatry 31 (suppl. 1):22–29. Bombardelli, E. and P. Morazzoni. 1995. Hypericum perforatum. Fitoterapia. 66(1):43–68. Brantner, A., T. Kartnig, F. Quehenberger. 1994. Vergleichende phytochemische Untersuchungen an Hypericum perforatum L. und Hypericum maculatum Crantz. Sci Pharm 62:261–276. Braun, R. et al. 1997. Standardzulassungen für Fertigarzneimittel--Text and Kommentar. Stuttgart: Deutscher Apotheker Verlag. British Herbal Pharmacopoeia (BHP). 1996. Exeter, U.K.: British Herbal Medicine Association. Bruneton, J. 1995. Pharmacognosy, Phytochemistry, Medicinal Plants. Paris: Lavoisier Publishing. Bühler. 1995. Communication from BfArM (German Federal Institute of Drugs and Medical Devices to German Nonprescription Drug Association (BAH), Sept. 11. Bundesanzeiger (BAnz). 1998. Monographien der Kommission E (Zulassungs- und Aufbereitungskommission am BGA für den humanmed. Bereich, phytotherapeutische Therapierichtung und Stoffgruppe). K"ln: Bundesgesundheitsamt (BGA). Butterweck, V., G. Jürgenliemk, A. Nahrstedt, H. Winterhoff. 1999. Flavonoid-Fraktionen und Hyperosid aus Hypericum perforatum L. zeigen anti-depressive Aktivität im Forced Swimming Test nach PORSOLT. Zeitschrift für Phytotherapie 20:86–87. Chatterjee, S.S., M. Noldner, E. Koch, C. Erdelmeier. 1998. Antidepressant activity of Hypericum perforatum and Hyperforin: the neglected possibility. Pharmacopsychiatry 31 (suppl. 1):7–15. Cott, J.M. 1999. Personal communication to M. Blumenthal, Aug. 27. Cott, J.M. and A. Fugh-Berman. 1998. Is St. John's Wort (Hypericum perforatum) an effective antidepressant? J Nerv Ment Dis 186(8):500–501. Cott, J.M. 1997. In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract. Pharmacopsychiatry 30 (suppl. 2):108–112. De Smet, P.A. and W.A. Nolen. 1996. St. John's wort as an antidepressant. BMJ 313(7052):241–242. Deutscher Arzneimittel-Codex (DAC). 1986. Stuttgart: Deutscher Apotheker Verlag. J010/1–5. Deutscher Arzneimittel-Codex, 3rd suppl. (DAC). 1991. Stuttgart: Deutscher Apotheker Verlag. Ellingwood, F. 1983. American Materia Medica, Therapeutics and Pharmacognosy. Portland, OR: Eclectic Medical Publications [reprint of 1919 original]. ESCOP. 1997. "Hyperici Herba." Monographs on the Medicinal Uses of Plant Drugs. Exeter, U.K.: European Scientific Cooperative on Phytotherapy. Felter, H.W. 1985. The Eclectic Materia Medica, Pharmacology and Therapeutics Portland, OR: Eclectic Medical Publications [reprint of the 1922 original]. 424. Felter, H.W. and J.U. Lloyd. 1983. King's American Dispensatory, 18th ed., 3rd rev. Portland, OR: Eclectic Medical Publications [reprint of 1898 original]. 1083–1039. Fugh-Berman A. and J.M. Cott. 1999. Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med (in press, Sept.; Oct.). Hänsgen, K.D., J. Vesper, M. Ploch. 1994. Multicenter double-blind study examining the antidepressant effectiveness of the Hypericum extract LI 160. J Geriatr Psychiatr Neurol 7(suppl. 1):S15–S18. Hobbs, C. 1989. St. John's wort: Hypericum perforatum L. A review. HerbalGram 18/19:24–33. ------. 1990. St. John's wort--ancient herbal protector. Pharmacy History 32(4):166. Hübner, W.D., S. Lande, H. Podzuweit. 1994. Hypericum treatment of mild depressions with somatic symptoms. J Geriatr Psychiatr Neurol 7(suppl. 1):S12–S14. Karnick, C.R. 1994. Pharmacopoeial Standards of Herbal Plants, Vols. 1–2. Delhi: Sri Satguru Publications. Vol. 1:189–192; Vol. 2:125. Kasper, S. 1997. Treatment of seasonal affective disorder (SAD) with Hypericum Extract. Pharmacopsych 30:S89–93. King, J. 1866. The American Dispensatory, 7th ed. Cincinnati: Moore, Wilstach, & Baldwin. Kneipp®, 1996. Wegweiser zu den Kneipp® Mitteln [Guide to Kneipp® Remedies]. Würzburg: Sebastian Kneipp Gesundheitsmittel-Verlag. 48–49, 168, 172. Kugler, J. W. et al. 1990. Therapie depressiver Zustände. Hypericum-Extrakt Steigerwald als Alternative zur Benzodiazepin-Behandlung. Z Allg Med 66:21–29. Laakmann, G., A. Deniel, M. Kieser. 1998a. Clinical significance of Hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities. Phytomedicine 5(6):435–442. Laakmann, G., C. Schule, T. Baghai, M. Kieser. 1998b. St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry 31(suppl. 1):54–59. Lange, D. and U. Schippmann. 1997. Trade Survey of Medicinal Plants in Germany--A Contribution to International Plant Species Conservation. Bonn: Bundesamt für Naturschutz. 29–35. Leung, A.Y. and S. Foster. 1996. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics, 2nd ed. New York: John Wiley & Sons, Inc. Linde, K. et al. 1996. St. John's wort for depression--an overview and meta-analysis of randomised clinical trials. BMJ 313(7052):253–258. McGuffin, M., C. Hobbs, R. Upton, A. Goldberg. 1997. American Herbal Product Association's Botanical Safety Handbook. Boca Raton: CRC Press. Meyer-Buchtela, E. 1999. Tee-Rezepturen--Ein Handbuch für Apotheker und Ärzte. Stuttgart: Deutscher Apotheker Verlag. Nadkarni, K.M. 1976. Indian Materia Medica. Bombay: Popular Prakashan. 673. Newall, C.A., L.A. Anderson, J.D. Phillipson. 1996. Herbal Medicines: A Guide for Health-Care Professionals. London: The Pharmaceutical Press. Okpanyi, S.N. and M.L. Weischer. 1987. Tierexperimentelle untersuchungen zur psychotropen wirksamkeit eines Hypericum-extraktes [Animal experiments on the psychotropic action of a Hypericum extract]. Arzneimittelforschung 37:10–13. Pharmacopée Française Xe Édition (Ph.Fr.X). 1983–1990. Moulins-les-Metz: Maisonneuve S.A. Pickering, C. 1879. Chronological History of Plants. Boston: Little Brown & Co. Rasmussen, P. 1998. St. John's wort--A review of its use in depression. Australian J Med Herbalism 10(1):8–13. Reuter, H.D. 1995. St. John's wort as a herbal antidepressant. Eur J Herbal Med Part I:1(3):19–24; Part II:1(4):15–21. ------. 1998. In: Lawson, L.D. and R. Bauer (eds.). 1998. Phytomedicines of Europe--Chemistry and Biological Activity. Washington, D.C.: American Chemical Society. 287–298. Reynolds, J.E.F. (ed.). 1993. Martindale: The Extra Pharmacopoeia, 30th ed. London: The Pharmaceutical Press. Schilcher, H. 1997. Phytotherapy in Pediatrics--Handbook for Physicians and Pharmacists. Stuttgart: Medpharm Scientific Publishers. 61–62. Schulz, V. 1998. Hyperforin values: By no means just "traces." [letter]. Deutsche Apotheker Zeitung 138(6). Schulz, V., W.D. Hübner, M. Ploch. 1997. Clinical trials with phyto-psychopharmacological agents. Phytomed 4(4):379–387. Schulz, H. and M. Jobert. 1993. Der Einfluss von Johanniskraut-Extrakt auf das Schlaf-EEG bei älteren Probandinnen. Nervenheilkunde 12:323–327. Schulz, V., R. Hänsel, V.E. Tyler. 1998. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. New York: Springer. 50–65. Staffeldt, B. et al. 1993. Pharmakokinetik von Hypericin und Pseudohypericin nach oraler Einnahme des Johanniskraut-Extraktes LI 160 bei gesunden Probanden. Nervenheilkunde 12:331–338. Snow, J.M. 1996. Hypericum perforatum L. (Hyperiaceae). Protocol J Botanical Med 2(1):16–21. State Pharmacopoeia of the Union of Soviet Socialist Republics, 10th ed. (USSR X). 1973. Moscow: Ministry of Health of the U.S.S.R. Upton, R. (ed.). 1997. St. John's Wort (Hypericum perforatum). American Herbal Pharmacopoeia (AHP). Santa Cruz: American Herbal Pharmacopoeia. 1–32 (published in HerbalGram 40). USP-DI Update. 1998. St. John's Wort and Powdered St. John's Wort. Rockville, MD: United States Pharmacopeia Convention, May. USP. 1999a. St. John's Wort and Powdered St. John's Wort. United States Pharmacopeia 24–National Formulary 19. Rockville, MD: United States Pharmacopeia Convention, Inc. USP. 1999b. Powdered St. John's wort extract monograph. Pharmacopeial Forum 25(2). USSR X. See State Pharmacopoeia of the Union of Soviet Socialist Republics. Weiser, D. 1991. Pharmakokinetik von Hypericin nach oraler Einnahme des Johanniskraut-Extraktes LI 160. Nervenheilkunde 10:318–319. Wichtl, M. and N.G. Bisset (eds.). 1994. Herbal Drugs and Phytopharmaceuticals. Stuttgart: Medpharm Scientific Publishers. Wonnemann, M., C. Schäfer, W.E. Müller. 1999. Johanniskrautextrakt: Effekte auf GABA- und glutamaterge Rezeptorsysteme. Zeitschrift für Phytotherapie 20:77–82. Additional Resources British Herbal Pharmacopoeia (BHP). 1983. Keighley, U.K.: British Herbal Medicine Association. Constantine, G.H. and J. Karchesy. 1999. Variations in Hypericin concentrations in Hypericum perforatum L. and commercial products. Pharm Biol 36(5):365–367. Cracchiolo, C. 1998. Pharmacology of St. John's wort: botanical and chemical aspects. Sci Rev Alt Med 2(1):29–35. Denke, A., W. Schneider, E.F. Elstner. 1999. Biochemical activities from Hypericum perforatum L.: 2nd Communication: Inhibition of metenkphaline- and tyrosine-dimerization. Arzneim-Forsch/Drug Res 49(2):109–114. Denke, A., H. Schempp, E.Mann, W. Schneider, E.F. Elstner. 1999. Biochemical activities from Hypericum perforatum L.: 4th communication: Influence of different cultivation methods. Arzneimforsch/Drug Res 49(2):120–125. Erdelmeier, C.A. 1998. Hyperforin, possibly the major non-nitrogenous secondary metabolite of Hypericum perforatum L. Pharmacopsych 31(suppl. 1):2–6. Gaedcke, F. 1997. Johanniskraut und dessen Zubereitungen. Deut Apoth Zeit No. 42/97. Grush, L.R., A. Nierenberg, B. Keefe, L.S. Cohen. 1998. St. John's wort during pregnancy [letter]. JAMA 280:1566. Halama, P. 1991. Wirksamkeit des Hypericum--Extraktes LI 160 bei 50 Patienten einer psychiatrischen Fachpraxis. Nervenheilkunde 10:305–307. Hänsel, R., K. Keller, H. Rimpler, G. Schneider (eds.). 1993. Hagers Handbuch der Pharmazeutischen Praxis, 5th ed. Vol. 5. Berlin-Heidelberg: Springer Verlag. 474–495. Hippius, H. 1998. St John's wort (Hypericum perforatum)--A herbal antidepressant. [in process citation]. Curr Med Res Opin 14(3):171–184. Kleber, E., T. Obry, S. Hippeli, W. Schneider, E.F. Elstner. 1999. Biochemical activities of extracts from Hypericum perforatum L. 1st Communication: Inhibition of dopamine-beta-hydroxylase. Arzneim-Forsch/Drug Research 49(2):106–109. Lust, J. 1974. The Herb Book. New York: Bantam Books. 344. Martinez, B., S. Kasper, S. Ruhrmann, H.J. Moller. 1994. Hypericum in the treatment of seasonal affective disorders. J Geriatr Psychiatry Neurol 7(suppl. 1):S29–S33. Mediherb, Pty. Ltd. 1996. Hypericum--New uses for an old wort. Mediherb Professional Newsletter Part 1:44, Part 2:45, Part 3:46. Müller, W.E. et al. 1998. Hyperforin represents the neuro-transmitter reuptake inhibiting constituent of Hypericum extract. Phamacopsych 31(suppl. 1):16–21. Müller, W.E., M. Rolli, C. Schafer, U. Hafner. 1997. Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry 30(suppl.):102–107. Norme Française (NF). 1989. NF T 75-348. Paris: Direction des Journaux Officiels. Reh, C., P. Laux, N. Schenk. 1992. Hypericum--Extrakt bei Depressionen--eine wirksame Alternative. Therapiewoche 42(25):1576–1581. Reuter, H.D. 1993. Hypericum als pflanzliches Antidepressivum. Z Phytother 14:239–254. Schellenberg, R., S. Sauer, W. Dimpfel. 1998. Pharmacodynamic effects of two different Hypericum extracts in healthy volunteers measured by quantitative EEG. Pharmacopsych 31 (suppl. 1):44–53. Schemp, H., A.Denke, E.Mann, W. Schneider, E.F. Elstner. 1999. Biochemical Activities from Hypericum perforatum L. 3rd communication: Modulation of peroxidase activity as a simple method for standardization. Arzneim-Forsch/Drug Res 49(2):115–119. Sharpley, A.L., C.L. McGavin, R. Whale, P.J. Cowen. 1998. Antidepressant-like effect of Hypericum perforatum (St John's wort) on the sleep polysomnogram. [in Process Citation]. Psychopharmacology (Berl) 139(3):286–287. Smyshliaeva, A.V. and IuB Kudriashov. 1992. Modifikatsiia luchevogo porazheniia zhivotnykh vodnym ekstraktom Hypericum perforatum L. Soobshchenie 1 [The modification of a radiation lesion in animals with an aqueous extract of Hypericum perforatum L. 1]. Biol Nauki (4):7–9. Sommer, H. 1991. Besserung psychovegetativer Beschwerden durch Hypericum im Rahmen einer multizentrischen Doppelblindstudie. Nervenheilkunde 10:308–310. Vorbach, E.U., K.H. Arnold, W.D. Hübner. 1997. Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10. Pharmacopsych 30(suppl.):81–85. Wheatley D. 1997. LI 160, an extract of St. John's wort, versus amitriptyline in mild to moderately depressed outpatients--a controlled 6-week clinical trial. Pharmacopsych 30(suppl.):77–80. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

St. John's wort (SJW) is a perennial herb native to Europe, North Africa, and western Asia. It has been introduced and naturalized in parts of Africa, Asia, Australia, and the Americas, and is found growing wild in neglected fields, dry pastures, rangelands, and along country roads (Bombardelli and Morazzoni, 1995; Leung and Foster, 1996; Snow, 1996; Upton, 1997; Wichtl and Bisset, 1994). In European medicine, SJW was traditionally obtained from Eastern European countries, where it is still wild collected (BHP, 1996; Braun et al., 1997; Wichtl and Bisset, 1994). It is cultivated in at least four provinces in Germany (Lange and Schippmann, 1997). The SJW used in Indian Ayurvedic medicine is distributed in the temperate western Himalayas, Kashmir, and Simla (Karnick, 1994; Nadkarni, 1976). SJW was initially brought to the northeastern United States by European colonists (Pickering, 1879; Upton, 1997). It is harvested from naturalized plants in the Pacific Northwest and eastern states (Upton, 1997). Since the mid-1990s, in order to meet new demands on supply, it has been quickly brought into large-scale cultivation in Europe, North and South America, Australia, and China. Many of SJW's therapeutic applications (except antiviral use), including its uses as a vulnerary, diuretic, and treatment for neuralgic conditions, stem from traditional Greek medicine, originally documented by ancient Greek medical herbalists Hippocrates (ca. 460–377 B.C.E.), Theophrastus (ca. 372–287 B.C.E.), Dioscorides (first century C.E.), and Galen (ca. 130–200 C.E.) (Bombardelli and Morazzoni, 1995; Hobbs, 1990; Leung and Foster, 1996; Upton, 1997). Since the time of Swiss physician Paracelsus (ca. 1493–1541 C.E.) it has been used to treat psychiatric disorders. At that time it was described as "arnica for the nerves" (Reuter, 1998). The aerial flowering parts of SJW have been used in traditional European medicine for centuries to treat neuralgia, anxiety, neurosis, and depression (Rasmussen, 1998). The traditional way to take SJW was as herbal tea, an aqueous extract whose single dose corresponded to 2–3 g of dried crude drug (Schulz et al., 1997). In the nineteenth and twentieth centuries, American Eclectic physicians prescribed SJW to treat hysteria and nervous affections with depression. It was prescribed externally to treat wounds, bruises, sprains, and much more (Ellingwood, 1983; Felter and Lloyd, 1983; Felter, 1985; King, 1866; Snow, 1996; Upton, 1997). Today, St. John's wort is official in the national pharmacopeias of Czechoslovakia, France, Poland, Romania, and Russia (Bruneton, 1995; Hobbs, 1989; Newall et al., 1996; Ph.Fr.X, 1990; Reynolds, 1993; Upton, 1997; USSR X, 1973). In Germany, SJW is listed in the German Drug Codex, approved as a medicine in the Commission E monographs, and licensed as a standard medicinal tea infusion (BAnz, 1998; Braun et al., 1997; DAC, 1991; Meyer-Buchtela, 1999; Schilcher, 1997; Wichtl and Bisset, 1994). It is used in psychiatric drugs in forms including dampoule (Hyperforat®), coated tablet (LI 160, Jarsin®, Lichtwer Pharma, Berlin), juice (Kneipp® Johanniskraut Pflanzensaft N), tea (Kneipp® Johanniskraut-Tee), and tincture (Psychotonin®M). It is used in some urological preparations affecting micturition (e.g., Inconturina®) (Kneipp®, 1996; Schilcher, 1997; Wichtl and Bisset, 1994). In German pediatric medicine, SJW aqueous infusions, alcoholic fluidextracts, and some proprietary products (such as Sedariston®, a combination of SJW and valerian (Valeriana officinalis) extracts) are used to treat depressive states in young people. For example, SJW is a component of a sedative tea for children, composed of 30% lemon balm leaf (Mellissa officinalis), 30% lavender flower (Lavandula officinalis), 30% passion flower herb (Passiflora spp.), and 10% SJW herb (Schilcher, 1997). In the United States it is used in a wide range of dietary supplements in forms including alcoholic tincture, aqueous infusion (oral), oil infusion (topical), and dry standardized extract in capsules and tablets (Leung and Foster, 1996; Upton, 1997). In 1998, the United States Pharmacopeia Drug Information division issued a therapeutic monograph and consumer information bulletin stating that the USP Advisory Panels do not recommend or support the use of SJW because they believe that there have not been enough quality studies to prove that it is effective. However, USP noted that research indicated the safety of SJW (USP-DI, 1998). The USP also published an identification monograph that included guidelines for assessing the identity and purity of raw material in bulk or powder form (USP, 1999a). Since 1979, there have been about 30 controlled trials with Hypericum extracts, involving thousands of patients with mild to moderate depressive disorders. Most studies lasted 28 to 42 days with daily dosages of 900 mg of an extract standardized to 0.3% hypericin (Jarsin®, LI 160, Lichtwer Pharma, Berlin). Up to 1997, there have been at least 15 controlled studies on a methanolic extract of SJW (LI 160) and 12 controlled studies on four additional preparations made from ethanolic extracts of SJW (Schulz et al., 1998). They have confirmed the antidepressant action of SJW extracts in humans (Bombardelli and Morazzoni, 1995; Linde et al., 1996; Reuter, 1998; Upton, 1997). These studies on SJW do not meet the criteria for conventional antidepressant drugs according to the regulatory guidelines of the European Union, thereby keeping SJW from being accepted for treatment for major depression (De Smet and Nolen, 1996). However, some of these same deficiencies relate to studies on conventional antidepressants when they are first marketed (Cott, 1999). Studies that compare treatment with SJW to treatment with a synthetic antidepressant have not lasted longer than six weeks and have been compared using about one-half the usual dose of the antidepressant (75 mg imipramine instead of 150 mg). In addition, they have not been conducted with severely depressed patients. Yet SJW has been shown to be safe, with very few side effects, compared with synthetic antidepressants: out of 3,250 patients, only allergic reactions (0.5%), gastrointestinal upset (0.6%), and fatigue (0.4%) were observed (De Smet and Nolen, 1996). Evidence of the antidepressant activity of SJW extracts can be found in reviews by Bombardelli and Morazzoni (1995), Linde et al. (1996), and Upton (1997). No significant modern human studies investigating SJW's other therapeutic uses have been found (e.g., orally for dyspeptic complaints and topically for burns, lesions, wounds, and myalgia). The constituents and mechanism of action responsible for the antidepressant properties of SJW have been investigated, with various authors citing different mechanisms (Bombardelli and Morazzoni, 1995; Rasmussen, 1998; Reuter, 1995, 1998). However, a recent randomized, double-blind, placebo-controlled, multicenter study on 147 male and female patients with mild to moderate depression indicated that hyperforin may be the primary active ingredient, or at least it plays a key role in the antidepressant activity. Patients received 300 mg of either a placebo, a SJW extract standardized to 0.5% hyperforin (WS 5573, W. Schwabe, Germany), or a SJW extract standardized to 5% hyperforin (WS 5572, Schwabe), three times daily for 42 days. While there was a reduction in depression scores in both the 0.5% hyperforin group and the placebo group, results were statistically significant for improvement of depressive symptoms only in the patients receiving the extract with 5% hyperforin (Laakmann et al., 1998a, 1998b). Of particular interest is the finding that patients with severe depression (n=56) experienced greater reduction of symptoms than mild to moderately depressed patients receiving the same dosage (although there is more room for improvement in severely depressed patients). The authors of this study concluded that the antidepressant activity of SJW is due to its hyperforin content. Other experimental studies have also shown the relevance of hyperforin (Chatterjee et al., 1998; Bhattacharya et al., 1998). However, additional animal and human research is being conducted to clarify the importance of hyperforin, since most of the studies on St. John's wort were conducted on preparations standardized to hypericin, not hyperforin, content. Nevertheless, a representative of the leading manufacturer of the most clinically tested hypericin-based SJW extract (i.e., LI 160 from Lichtwer Pharma) has written that this product showed hyperforin levels of 1% to 6% upon analysis; new studies by Lichtwer on LI 160 will be carried out on an extract standardized to hyperforin values of approximately 4% (Schulz, 1998). Although additional research is warranted, the modern therapeutic application of SJW for mild to moderate depression is supported by its history of use in traditional medicine, in vitro studies (Cott, 1997; Wonnemann et al., 1999), in vivo experiments in animals (Butterweck et al., 1999; Okpanyi and Weischer, 1987), pharmacodynamic studies in humans (Kugler et al., 1990; Schulz and Jobert, 1993), pharmacokinetic studies in humans (Staffeldt et al., 1993; Weiser, 1991), human clinical studies (Hänsgen et al., 1994; Hübner et al., 1994; Cott, 1997; Fugh-Berman and Cott, 1999), meta-analyses (Linde et al., 1996) and extensive phytochemical investigations (Bombardelli and Morazzoni, 1995; Brantner et al., 1994). A major three-year, multicenter clinical study on the antidepressant effect of SJW is being carried out in the United States under the auspices of the National Institutes of Health. This is the first clinical study to test SJW directly against a modern selective serotonin reuptake inhibitor (SSRI) (sertraline, Zoloft®) and placebo. The trial consists of 330 patients (110 in each arm--SJW, sertraline, placebo) and the duration of treatment will last six months, the longest trial on SJW to date. Patients are required to test a minimum of 20 points on the Hamilton Depression Scale, thus being classed as moderately to severely depressed. A small study has investigated the possible use of SJW for seasonal affective disorder (SAD), a condition of depressive mood associated with winter months and lack of sunlight (Kasper, 1997). In an open study, 22 patients diagnosed with SAD were given SJW extract (300 mg three times daily) with additional bright light or the same dose of SJW in dim light conditions. As determined by a standard method for measuring depression symptoms (Hamilton Depression Scale), subjects in both groups experienced a significant reduction in depression score, there being no difference in the bright and dim light groups. Therefore, no conclusion for the effectiveness of SJW in SAD can be drawn from the results of this study. Pharmacopeial grade SJW consists of the dried flowering tops or aerial parts of Hypericum perforatum L., harvested shortly before or during the flowering period. It must contain not less than 12% water soluble extractive. Botanical identity must be confirmed by thin-layer chromatography (TLC), macrocopic and microscopic examinations, and organoleptic (sensory) evaluation (BHP, 1996). The German Drug Codex additionally required not less than 0.4% dianthrones of the hypericin group, calculated as hypericin (DAC, 1986; Wichtl and Bisset, 1994). The German Standard License monograph requires the material to conform with the German Drug Codex requirements (Braun et al., 1997). However, the German Federal Institute for Drugs and Medical Devices (BfArM) declared that hypericin would no longer be used as a required marker compound for the chemical standardization of St. John's wort (Bühler, 1995). The United States Pharmacopeia requires not less than 0.2% of hypericin and pseudohypericin combined and not less than 3.0% of hyperforin (USP, 1999b). The ESCOP monograph requires the material to conform with either the French Pharmacopoeia or the German Drug Codex (ESCOP, 1997). Description St. John's wort consists of the dried, aboveground parts of H. perforatum L. [Fam. Hypericaceae], gathered during flowering season, and their preparations in effective dosage. Chemistry and Pharmacology St. John's wort herb contains 6.5–15% catechin-type tannins and condensed-type proanthocyanidins (catechin, epicatechin, leucocyanidin); 2–5% flavonoids, mostly hyperoside (0.5–2%), rutin (0.3–1.6%), quercitrin (0.3%), isoquercitrin (0.3%), quercetin, and kaempferol; biflavonoids (approximately 0.26% biapigenin); phloroglucinol derivatives (up to 4% hyperforin); phenolic acids (caffeic, chlorogenic, ferulic); 0.05–1.0% volatile oils, mainly higher n-alkanes; 0.05–0.15% naphthodianthrones (hypericin and pseudohypericin); sterols (b-sitosterol); vitamins C and A; xanthones (up to 10 ppm); and choline (Bruneton, 1995; ESCOP, 1997; Leung and Foster, 1996; Newall et al., 1996; Wichtl and Bisset, 1994). The Commission E reported that a mild antidepressant action of the herb and its preparations has been observed and reported by many physicians. Although the Commission E categorized St. John's wort as an MAO inhibitor, this was based on in vitro research and not conducted in animal systems. Subsequent research has indicated either no or very slight MAO activity in St. John's wort or its preparations. The Commission E recognized the anti-inflammatory action of topical oily Hypericum preparations. The British Herbal Pharmacopoeia reported antidepressant action (BHP, 1996). In numerous controlled double-blind and open studies using hydroalcoholic SJW preparations, a significant improvement of mood, and loss of interest and activity and other depressive syndrome symptoms, such as sleep, concentration, and somatic complaints, has been reported (ESCOP, 1997). Uses In December 1984, the Commission E approved the internal use of St. John's wort for psychovegetative (psychoautonomic) disturbances, depressive moods, anxiety, and nervous unrest. Oily Hypericum preparations are approved for dyspeptic complaints. External use of oily preparations of St. John's wort is approved for treatment and post-therapy of acute and contused injuries, myalgia, and first-degree burns. ESCOP indicates its use for mild to moderate depressive states, restlessness, anxiety, and irritability (ESCOP, 1997). The German Standard License for St. John's wort tea lists it for nervous excitement and sleep disturbances (Wichtl and Bisset, 1994). With the exception of its antiviral use, other modern applications date back two thousand years (Hobbs, 1990). Since the 1984 monograph was based on general clinical use and only one clinical study (out of more than 27 that had been published up to 1997) had been published at that time, the Commission was relatively accurate in its evaluation of the therapeutic effects of SJW. However, given that most the recent research has focused on antidepressant activity of SJW, it is reasonable to conclude that this use should be the only primary use, when administered in proper form and dosage (Schulz et al., 1998). SJW may benefit the other uses (psychovegetative disturbances, anxiety, and nervous unrest) only within the framework of its general antidepressant activity (Schulz et al., 1998). Contraindications None known. Side Effects Commission E noted that photosensitization is possible, especially in fair-skinned individuals. However, animal and human research has indicated that photosensitization is not likely to occur at the recommended dosage levels. Based on experimental studies (animal and human), it would take approximately 30 to 50 times the recommended daily dose of 900 mg of the standardized extract to produce severe phototoxic effects in humans (Schulz et al., 1998). Use During Pregnancy and Lactation No restrictions known (McGuffin et al., 1997). Interactions with Other Drugs Commission E reported that none were known (in 1984). ESCOP also noted that none were reported (ESCOP, 1997). Dosage and Administration The original Commission E monograph (1984) noted the following dosage: "Unless otherwise prescribed: 2–4 g per day of chopped or powdered herb for internal use, or 0.2–1 mg of total hypericin in other forms of preparation application. Liquid and semi-solid preparations for external use. Preparations made with fatty oils for external and internal use." Although the original Commission E monograph specified minimum levels of hypericin, this is no longer required on the label of German products (Ahuis, 1998). In Germany, the current required dosage is 300 mg, three times daily of a hydroalcoholic St. John's wort extract. The registration for infusions (tea) of St. John's wort has recently been withdrawn due to a lack of evidence of efficacy (BfArM, 1998). Based on the available research, the approved effective equivalent preparations are as follows: Internal: Fluidextract 1:1 (g/ml): 2 ml, twice daily. Native dry extract 5–7:1: 300 mg, three times daily. External: Oily macerate (Oleum hyperici): macerate fresh flowering tops in olive oil or wheat-germ oil for several weeks, stirring often; strain through a cloth and press pulp; for direct application to affected areas. References Ahuis, F. 1998. Neues über Johanniskraut [News on St. John's Wort]. Deutsche Apotheker Zeitung 138:1783–1785. BAnz. See Bundesanzeiger. BfArM. 1998. Meeting of BfArM, Johanniskraut, No. 113. BPI [Federal Manufacturers Association]. 151. Bhattacharya, S.K., A. Chakrabarti, S.S. Chatterjee. 1998. Activity profiles of two hyperforin-containing Hypericum extracts in behavioral models. Pharmacopsychiatry 31 (suppl. 1):22–29. Bombardelli, E. and P. Morazzoni. 1995. Hypericum perforatum. Fitoterapia. 66(1):43–68. Brantner, A., T. Kartnig, F. Quehenberger. 1994. Vergleichende phytochemische Untersuchungen an Hypericum perforatum L. und Hypericum maculatum Crantz. Sci Pharm 62:261–276. Braun, R. et al. 1997. Standardzulassungen für Fertigarzneimittel--Text and Kommentar. Stuttgart: Deutscher Apotheker Verlag. British Herbal Pharmacopoeia (BHP). 1996. Exeter, U.K.: British Herbal Medicine Association. Bruneton, J. 1995. Pharmacognosy, Phytochemistry, Medicinal Plants. Paris: Lavoisier Publishing. Bühler. 1995. Communication from BfArM (German Federal Institute of Drugs and Medical Devices to German Nonprescription Drug Association (BAH), Sept. 11. Bundesanzeiger (BAnz). 1998. Monographien der Kommission E (Zulassungs- und Aufbereitungskommission am BGA für den humanmed. Bereich, phytotherapeutische Therapierichtung und Stoffgruppe). K"ln: Bundesgesundheitsamt (BGA). Butterweck, V., G. Jürgenliemk, A. Nahrstedt, H. Winterhoff. 1999. Flavonoid-Fraktionen und Hyperosid aus Hypericum perforatum L. zeigen anti-depressive Aktivität im Forced Swimming Test nach PORSOLT. Zeitschrift für Phytotherapie 20:86–87. Chatterjee, S.S., M. Noldner, E. Koch, C. Erdelmeier. 1998. Antidepressant activity of Hypericum perforatum and Hyperforin: the neglected possibility. Pharmacopsychiatry 31 (suppl. 1):7–15. Cott, J.M. 1999. Personal communication to M. Blumenthal, Aug. 27. Cott, J.M. and A. Fugh-Berman. 1998. Is St. John's Wort (Hypericum perforatum) an effective antidepressant? J Nerv Ment Dis 186(8):500–501. Cott, J.M. 1997. In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract. Pharmacopsychiatry 30 (suppl. 2):108–112. De Smet, P.A. and W.A. Nolen. 1996. St. John's wort as an antidepressant. BMJ 313(7052):241–242. Deutscher Arzneimittel-Codex (DAC). 1986. Stuttgart: Deutscher Apotheker Verlag. J010/1–5. Deutscher Arzneimittel-Codex, 3rd suppl. (DAC). 1991. Stuttgart: Deutscher Apotheker Verlag. Ellingwood, F. 1983. American Materia Medica, Therapeutics and Pharmacognosy. Portland, OR: Eclectic Medical Publications [reprint of 1919 original]. ESCOP. 1997. "Hyperici Herba." Monographs on the Medicinal Uses of Plant Drugs. Exeter, U.K.: European Scientific Cooperative on Phytotherapy. Felter, H.W. 1985. The Eclectic Materia Medica, Pharmacology and Therapeutics Portland, OR: Eclectic Medical Publications [reprint of the 1922 original]. 424. Felter, H.W. and J.U. Lloyd. 1983. King's American Dispensatory, 18th ed., 3rd rev. Portland, OR: Eclectic Medical Publications [reprint of 1898 original]. 1083–1039. Fugh-Berman A. and J.M. Cott. 1999. Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med (in press, Sept.; Oct.). Hänsgen, K.D., J. Vesper, M. Ploch. 1994. Multicenter double-blind study examining the antidepressant effectiveness of the Hypericum extract LI 160. J Geriatr Psychiatr Neurol 7(suppl. 1):S15–S18. Hobbs, C. 1989. St. John's wort: Hypericum perforatum L. A review. HerbalGram 18/19:24–33. ------. 1990. St. John's wort--ancient herbal protector. Pharmacy History 32(4):166. Hübner, W.D., S. Lande, H. Podzuweit. 1994. Hypericum treatment of mild depressions with somatic symptoms. J Geriatr Psychiatr Neurol 7(suppl. 1):S12–S14. Karnick, C.R. 1994. Pharmacopoeial Standards of Herbal Plants, Vols. 1–2. Delhi: Sri Satguru Publications. Vol. 1:189–192; Vol. 2:125. Kasper, S. 1997. Treatment of seasonal affective disorder (SAD) with Hypericum Extract. Pharmacopsych 30:S89–93. King, J. 1866. The American Dispensatory, 7th ed. Cincinnati: Moore, Wilstach, & Baldwin. Kneipp®, 1996. Wegweiser zu den Kneipp® Mitteln [Guide to Kneipp® Remedies]. Würzburg: Sebastian Kneipp Gesundheitsmittel-Verlag. 48–49, 168, 172. Kugler, J. W. et al. 1990. Therapie depressiver Zustände. Hypericum-Extrakt Steigerwald als Alternative zur Benzodiazepin-Behandlung. Z Allg Med 66:21–29. Laakmann, G., A. Deniel, M. Kieser. 1998a. Clinical significance of Hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities. Phytomedicine 5(6):435–442. Laakmann, G., C. Schule, T. Baghai, M. Kieser. 1998b. St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry 31(suppl. 1):54–59. Lange, D. and U. Schippmann. 1997. Trade Survey of Medicinal Plants in Germany--A Contribution to International Plant Species Conservation. Bonn: Bundesamt für Naturschutz. 29–35. Leung, A.Y. and S. Foster. 1996. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics, 2nd ed. New York: John Wiley & Sons, Inc. Linde, K. et al. 1996. St. John's wort for depression--an overview and meta-analysis of randomised clinical trials. BMJ 313(7052):253–258. McGuffin, M., C. Hobbs, R. Upton, A. Goldberg. 1997. American Herbal Product Association's Botanical Safety Handbook. Boca Raton: CRC Press. Meyer-Buchtela, E. 1999. Tee-Rezepturen--Ein Handbuch für Apotheker und Ärzte. Stuttgart: Deutscher Apotheker Verlag. Nadkarni, K.M. 1976. Indian Materia Medica. Bombay: Popular Prakashan. 673. Newall, C.A., L.A. Anderson, J.D. Phillipson. 1996. Herbal Medicines: A Guide for Health-Care Professionals. London: The Pharmaceutical Press. Okpanyi, S.N. and M.L. Weischer. 1987. Tierexperimentelle untersuchungen zur psychotropen wirksamkeit eines Hypericum-extraktes [Animal experiments on the psychotropic action of a Hypericum extract]. Arzneimittelforschung 37:10–13. Pharmacopée Française Xe Édition (Ph.Fr.X). 1983–1990. Moulins-les-Metz: Maisonneuve S.A. Pickering, C. 1879. Chronological History of Plants. Boston: Little Brown & Co. Rasmussen, P. 1998. St. John's wort--A review of its use in depression. Australian J Med Herbalism 10(1):8–13. Reuter, H.D. 1995. St. John's wort as a herbal antidepressant. Eur J Herbal Med Part I:1(3):19–24; Part II:1(4):15–21. ------. 1998. In: Lawson, L.D. and R. Bauer (eds.). 1998. Phytomedicines of Europe--Chemistry and Biological Activity. Washington, D.C.: American Chemical Society. 287–298. Reynolds, J.E.F. (ed.). 1993. Martindale: The Extra Pharmacopoeia, 30th ed. London: The Pharmaceutical Press. Schilcher, H. 1997. Phytotherapy in Pediatrics--Handbook for Physicians and Pharmacists. Stuttgart: Medpharm Scientific Publishers. 61–62. Schulz, V. 1998. Hyperforin values: By no means just "traces." [letter]. Deutsche Apotheker Zeitung 138(6). Schulz, V., W.D. Hübner, M. Ploch. 1997. Clinical trials with phyto-psychopharmacological agents. Phytomed 4(4):379–387. Schulz, H. and M. Jobert. 1993. Der Einfluss von Johanniskraut-Extrakt auf das Schlaf-EEG bei älteren Probandinnen. Nervenheilkunde 12:323–327. Schulz, V., R. Hänsel, V.E. Tyler. 1998. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. New York: Springer. 50–65. Staffeldt, B. et al. 1993. Pharmakokinetik von Hypericin und Pseudohypericin nach oraler Einnahme des Johanniskraut-Extraktes LI 160 bei gesunden Probanden. Nervenheilkunde 12:331–338. Snow, J.M. 1996. Hypericum perforatum L. (Hyperiaceae). Protocol J Botanical Med 2(1):16–21. State Pharmacopoeia of the Union of Soviet Socialist Republics, 10th ed. (USSR X). 1973. Moscow: Ministry of Health of the U.S.S.R. Upton, R. (ed.). 1997. St. John's Wort (Hypericum perforatum). American Herbal Pharmacopoeia (AHP). Santa Cruz: American Herbal Pharmacopoeia. 1–32 (published in HerbalGram 40). USP-DI Update. 1998. St. John's Wort and Powdered St. John's Wort. Rockville, MD: United States Pharmacopeia Convention, May. USP. 1999a. St. John's Wort and Powdered St. John's Wort. United States Pharmacopeia 24–National Formulary 19. Rockville, MD: United States Pharmacopeia Convention, Inc. USP. 1999b. Powdered St. John's wort extract monograph. Pharmacopeial Forum 25(2). USSR X. See State Pharmacopoeia of the Union of Soviet Socialist Republics. Weiser, D. 1991. Pharmakokinetik von Hypericin nach oraler Einnahme des Johanniskraut-Extraktes LI 160. Nervenheilkunde 10:318–319. Wichtl, M. and N.G. Bisset (eds.). 1994. Herbal Drugs and Phytopharmaceuticals. Stuttgart: Medpharm Scientific Publishers. Wonnemann, M., C. Schäfer, W.E. Müller. 1999. Johanniskrautextrakt: Effekte auf GABA- und glutamaterge Rezeptorsysteme. Zeitschrift für Phytotherapie 20:77–82. Additional Resources British Herbal Pharmacopoeia (BHP). 1983. Keighley, U.K.: British Herbal Medicine Association. Constantine, G.H. and J. Karchesy. 1999. Variations in Hypericin concentrations in Hypericum perforatum L. and commercial products. Pharm Biol 36(5):365–367. Cracchiolo, C. 1998. Pharmacology of St. John's wort: botanical and chemical aspects. Sci Rev Alt Med 2(1):29–35. Denke, A., W. Schneider, E.F. Elstner. 1999. Biochemical activities from Hypericum perforatum L.: 2nd Communication: Inhibition of metenkphaline- and tyrosine-dimerization. Arzneim-Forsch/Drug Res 49(2):109–114. Denke, A., H. Schempp, E.Mann, W. Schneider, E.F. Elstner. 1999. Biochemical activities from Hypericum perforatum L.: 4th communication: Influence of different cultivation methods. Arzneimforsch/Drug Res 49(2):120–125. Erdelmeier, C.A. 1998. Hyperforin, possibly the major non-nitrogenous secondary metabolite of Hypericum perforatum L. Pharmacopsych 31(suppl. 1):2–6. Gaedcke, F. 1997. Johanniskraut und dessen Zubereitungen. Deut Apoth Zeit No. 42/97. Grush, L.R., A. Nierenberg, B. Keefe, L.S. Cohen. 1998. St. John's wort during pregnancy [letter]. JAMA 280:1566. Halama, P. 1991. Wirksamkeit des Hypericum--Extraktes LI 160 bei 50 Patienten einer psychiatrischen Fachpraxis. Nervenheilkunde 10:305–307. Hänsel, R., K. Keller, H. Rimpler, G. Schneider (eds.). 1993. Hagers Handbuch der Pharmazeutischen Praxis, 5th ed. Vol. 5. Berlin-Heidelberg: Springer Verlag. 474–495. Hippius, H. 1998. St John's wort (Hypericum perforatum)--A herbal antidepressant. [in process citation]. Curr Med Res Opin 14(3):171–184. Kleber, E., T. Obry, S. Hippeli, W. Schneider, E.F. Elstner. 1999. Biochemical activities of extracts from Hypericum perforatum L. 1st Communication: Inhibition of dopamine-beta-hydroxylase. Arzneim-Forsch/Drug Research 49(2):106–109. Lust, J. 1974. The Herb Book. New York: Bantam Books. 344. Martinez, B., S. Kasper, S. Ruhrmann, H.J. Moller. 1994. Hypericum in the treatment of seasonal affective disorders. J Geriatr Psychiatry Neurol 7(suppl. 1):S29–S33. Mediherb, Pty. Ltd. 1996. Hypericum--New uses for an old wort. Mediherb Professional Newsletter Part 1:44, Part 2:45, Part 3:46. Müller, W.E. et al. 1998. Hyperforin represents the neuro-transmitter reuptake inhibiting constituent of Hypericum extract. Phamacopsych 31(suppl. 1):16–21. Müller, W.E., M. Rolli, C. Schafer, U. Hafner. 1997. Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry 30(suppl.):102–107. Norme Française (NF). 1989. NF T 75-348. Paris: Direction des Journaux Officiels. Reh, C., P. Laux, N. Schenk. 1992. Hypericum--Extrakt bei Depressionen--eine wirksame Alternative. Therapiewoche 42(25):1576–1581. Reuter, H.D. 1993. Hypericum als pflanzliches Antidepressivum. Z Phytother 14:239–254. Schellenberg, R., S. Sauer, W. Dimpfel. 1998. Pharmacodynamic effects of two different Hypericum extracts in healthy volunteers measured by quantitative EEG. Pharmacopsych 31 (suppl. 1):44–53. Schemp, H., A.Denke, E.Mann, W. Schneider, E.F. Elstner. 1999. Biochemical Activities from Hypericum perforatum L. 3rd communication: Modulation of peroxidase activity as a simple method for standardization. Arzneim-Forsch/Drug Res 49(2):115–119. Sharpley, A.L., C.L. McGavin, R. Whale, P.J. Cowen. 1998. Antidepressant-like effect of Hypericum perforatum (St John's wort) on the sleep polysomnogram. [in Process Citation]. Psychopharmacology (Berl) 139(3):286–287. Smyshliaeva, A.V. and IuB Kudriashov. 1992. Modifikatsiia luchevogo porazheniia zhivotnykh vodnym ekstraktom Hypericum perforatum L. Soobshchenie 1 [The modification of a radiation lesion in animals with an aqueous extract of Hypericum perforatum L. 1]. Biol Nauki (4):7–9. Sommer, H. 1991. Besserung psychovegetativer Beschwerden durch Hypericum im Rahmen einer multizentrischen Doppelblindstudie. Nervenheilkunde 10:308–310. Vorbach, E.U., K.H. Arnold, W.D. Hübner. 1997. Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10. Pharmacopsych 30(suppl.):81–85. Wheatley D. 1997. LI 160, an extract of St. John's wort, versus amitriptyline in mild to moderately depressed outpatients--a controlled 6-week clinical trial. Pharmacopsych 30(suppl.):77–80. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

Ok heres the real 411 on St. Johns Wort Originally it was thought that the action of St. John's wort extract as an antidepressant was due to hypericin acting as an inhibitor of the enzyme monoamine oxidase (MAO) - thereby resulting in the increase of CNS monoamines such as serotonin and dopamine. However, newer information indicates that St. John's wort possesses no in vivo inhibition of MAO.3,4 At least two other mechanisms have been proposed: modulation of interleukin-6 activity and inhibition of the re-uptake of serotonin. The modulating effects of St. John's wort extract on interleukin-6 (IL-6) is the most interesting as it proposes a mechanism by which St. John's wort interacts with the link between the immune system and mood. The immune system and the nervous system share many common biochemical features and regulatory interactions. In regards to IL-6, this cytokine is heavily involved in the communication between cells within and outside the immune system. In relationship to the nervous system, IL-6 is known to modulate hypothalamic-pituitary-end organ axes, especially the hypothalamic-pituitary-adrenal (HPA) axis. The hypothesis is that an elevation in IL-6 results in activation of the HPA axis leading to elevations in CRH and other adrenal regulatory hormones - hallmark features in depression. St. John's wort extract has shown an ability to reduce IL-6 levels, hence this action may explain the clinical effectiveness of St. John's wort extract.5 St. John's wort extract has also been shown to inhibit the re-uptake of serotonin similar in fashion to drugs like fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft). The study demonstrating a 50% serotonin re-uptake inhibition utilized the 0.3% hypericin content standardized extract at a concentration of 6.2 mcg/ml and did not attempt to identify the active inhibitors.6 Even though the authors of the study concluded "that the antidepressant activity of Hypericum extract is due to inhibition of serotonin uptake by postsynaptic receptors." An important point must be made - until pharmacokinetic studies demonstrate that St. John's wort components pass across the blood-brain barrier a primary site of action outside the central nervous system cannot be ruled out. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

St Johns Wort is an anti-depressant. If you are looking to build up seratonin reserves then try 5-HTP. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

I personally like mdma better, only cos its an empathogen. I like the lovey dovey feeling from it. mda you really don't get any of it. it all depends who i am with and what i am doing. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

Too lazy to discuss it, but here is a PIHKAL entry for mda. #100 MDA 3,4-METHYLENEDIOXYAMPHETAMINE SYNTHESIS: (from piperonal) To a solution of 15.0 g piperonal in 80 mL glacial acetic acid there was added 15 mL nitroethane followed by 10 g cyclohexylamine. The mixture was held at steam-bath temperature for 6 h, diluted with 10 mL H2O, seeded with a crystal of product, and cooled overnight at 10 °C. The bright yellow crystals were removed by filtration, and air dried to yield 10.7 g of 1-(3,4-methylenedioxyphenyl)-2-nitropropene with a mp of 93-94 °C. This was raised to 97-98 °C by recrystallization from acetic acid. The more conventional efforts of nitrostyrene synthesis using an excess of nitroethane as a solvent and anhydrous ammonium acetate as the base, gives impure product in very poor yields. The nitrostyrene has been successfully made from the components in cold MeOH, with aqueous NaOH as the base. A suspension of 20 g LAH in 250 mL anhydrous THF was placed under an inert atmosphere and stirred magnetically. There was added, dropwise, 18 g of 1-(3,4-methylenedioxyphenyl)-2-nitropropene in solution in THF and the reaction mixture was maintained at reflux for 36 h. After being brought back to room temperature, the excess hydride was destroyed with 15 mL IPA, followed by 15 mL of 15% NaOH. An additional 50 mL H2O was added to complete the conversion of the aluminum salts to a loose, white, easily filtered solid. This was removed by filtration, and the filter cake washed with additional THF. The combined filtrate and washes were stripped of solvent under vacuum, and the residue dissolved in dilute H2SO4. Washing with 3x75 mL CH2Cl2 removed much of the color, and the aqueous phase was made basic and reextracted with 3x100 mL CH2Cl2. Removal of the solvent yielded 13.0 g of a yellow-colored oil that was distilled. The fraction boiling at 80-90 °C at 0.2 mm weighed 10.2 g and was water-white. It was dissolved in 60 mL of IPA, neutralization with concentrated HCl, and diluted with 120 mL of anhydrous Et2O which produced a lasting turbidity. Crystals formed spontaneously which were removed by filtration, washed with Et2O, and air dried to provide 10.4 g of 3,4-methylenedioxyamphetamine hydrochloride (MDA) with a mp of 187-188 °C. (from 3,4-methylenedioxyphenylacetone) To a solution of 32.5 g anhydrous ammonium acetate in 120 mL MeOH, there was added 7.12 g 3,4-methylenedioxyphenylacetone (see under MDMA for its preparation) followed by 2.0 g sodium cyanoborohydride. The resulting yellow solution was vigorously stirred, and concentrated HCl was added periodically to keep the pH of the reaction mixture between 6 and 7 as determined by external damp universal pH paper. After several days, undissolved solids remained in the reaction mixture and no more acid was required. The reaction mixture was added to 600 mL of dilute HCl, and this was washed with 3x100 mL CH2Cl2. The combined washes were back-extracted with a small amount of dilute HCl, the aqueous phases combined, and made basic with 25% NaOH. This was then extracted with 3x100 mL CH2Cl2, these extracts combined, and the solvent removed under vacuum to provide 3.8 g of a red-colored residue. This was distilled at 80-90 °C at 0.2 mm/Hg to provide 2.2 g of an absolutely water-white oil. There was no obvious formation of a carbonate salt when exposed to air. This was dissolved in 15 mL IPA, neutralized with 25 drops of concentrated HCl, and diluted with 30 mL anhydrous Et2O. Slowly there was the deposition of white crystals of 3,4-methylenedioxyamphetamine hydrochloride (MDA) which weighed 2.2 g and had a mp of 187-188 °C. The preparation of the formamide (a precursor to MDMA) and the acetamide (a precursor to MDE) are described under those entries. DOSAGE: 80 - 160 mg. DURATION: 8 - 12 h. QUALITATIVE COMMENTS: (with 100 mg) The coming on was gradual and pleasant, taking from an hour to an hour and one half to do so. The trip was euphoric and intense despite my having been naturally depleted from a working day and having started so late. One thing that impressed itself upon me was the feeling I got of seeing the play of events, of what I thought to be the significance of certain people coming into my life, and why my `dance', like everyone else's, is unique. I saw that every encounter or event is a potential for growth, and an opportunity for me to realize my completeness at where I am, here and now, not at some future where I must lug the pieces of the past for a final assemblage `there.' I was reminded of living the moment to its fullest and I felt that seeing this was indicative that I was on the right track. (with 128 mg) Forty-five minutes after the second dosage, when I was seated in a room by myself, not smoking, and where there was no possible source of smoke rings, an abundance of curling gray smoke rings was readily observed in the environment whenever a relaxed approach to subjective observation was used. Visually these had complete reality and it seemed quite unneccessary to test their properties because it was surely known and fully appreciated that the source of the visual phenomena could not be external to the body. When I concentrated my attention on the details of the curling gray forms by trying to note how they would be affected by passing a finger through their apparent field, they melted away. Then, when I relaxed again, the smoke rings were there. I was as certain that they were really there as I am now sure that my head is on top of my body. (with 140 mg) I vomited quite abruptly, and then everything was OK. I had been drinking probably excessively the last two days, and maybe the body needed to unpoison itself. The tactile sense is beautiful, but there seems to be some numbness as well, and I feel that nothing erotic would be do-able. Intimacy, yes, but no performance I'm pretty sure. I saw the experience start drifting away only four hours into it, and I was sad to see it go. It was an all around delightful day. (with 200 mg, 2x100 mg spaced 1 h) The first portion was apparent at one-half hour. There was microscopic nausea shortly after the second portion was taken, and in an hour there was a complete +++ developed. The relaxation was extreme. And there seemed to be time distortion, in that time seemed to pass slowly. There was a occasional LSD-like moment of profoundness, but by and large it was a simple intoxication with most things seeming quite hilarious. The intoxication was also quite extreme. Some food was tried later in the experiment, and it tasted good, but there was absolutely no appetite. None at all. (with 60 mg of the "R" isomer) There was a light and not too gentle development of a somewhat brittle wound-up state, a + or even a ++. Chills, and I had to get under an electric blanket to be comfortable. The effects smoothed out at the fourth hour, when things started to return to baseline. Not too entertaining. (with 100 mg of the "R" isomer) Rapid development from the 40 minute point to an hour and a quarter; largely a pleasant intoxication, but there is something serious there too. No great insights, and not too much interference with the day's goings-on. Completely clear at the 8 hour point. (with 120 mg of the "R" isomer) This is a stoning intoxicant. I would not choose to drive, because of possible judgement problems, but my handwriting seems to be clear and normal. The mental excitement dropped rapidly but I was aware of physical residues for several additional hours. (with 80 mg of the "S" isomer) A very thin, light threshold, which is quite delightful. I am quite willing to push this a bit higher. (with 120 mg of the "S" isomer) Perhaps to a one +. Very light, and very much like MDMA, but perhaps shorter lived. I am pretty much baseline in three hours. (with 160 mg of the "S" isomer) The development is very rapid, and there is both muscular tremor and some nausea. The physicals are quite bothersome. With eyes closed, there are no effects noticeable, but with eyes open, things are quite bright and sparkling. The muscular spasms persist, and there is considerable teeth clenching. I feel that the mental is not worth the physical. EXTENSIONS AND COMMENTARY: There are about twenty different synthetic routes in the literature for the preparation of MDA. Many start with piperonal, and employ it to make methylenedioxyphenylacetone or a methylenedioxydihydro-cinnamic acid amide instead of the nitrostyrene. The phenylacetone can be reduced in several ways other than the cyanoborohydride method mentioned here, and the amide can be rearranged directly to MDA. And there are additional methods for the reduction of the nitrostyrene that use no lithium aluminum hydride. Also there are procedures that have safrole or isosafrole as starting points. There is even one in the underground literature that starts with sassafras root bark. In fact, it is because safrole is one of the ten essential oils that MDA can humorously be referred to as one of the Ten Essential Amphetamines. See the comments under TMA. There is a broad and checkered history concerning the use and abuse of MDA, and it is not the case that all the use was medical and all the abuse was social. One of the compulsive drives of both the military and the intelligence groups, just after World War II, was to discover and develop chemical agents which might serve as "truth serums" or as incapacitating agents. These government agencies considered the area of the psychedelics to be a fertile field for searching. The giving of relatively unexplored drugs in a cavalier manner to knowing and unknowing subjects was commonplace. There was one case in 1953, involving MDA and a psychiatric patient named Howard Blauer that proved fatal. The army had contracted with several physicians at the New York State Psychiatric Institute to explore new chemicals from the Edgewood Arsenal and one of these, with a chemical warfare code number of EA-1298, was MDA. The last and lethal injection into Blauer was an intravenous dose of 500 milligrams. There have been a number of medical explorations. Under the code SKF-5 (and trade name of Amphedoxamine) it was explored as an anorexic agent. It has been found promising in the treatment of psychoneurotic depression. There are several medical reports, and one book (Claudio Naranjo's The Healing Journey), that describe its values in psychotherapy. MDA was also one of the major drugs that was being popularly used in the late 1960's when the psychedelic concept exploded on the public scene. MDA was called the "hug-drug" and was said to stand for Mellow Drug of America. There was no difficulty in obtaining unending quantities of it, as it was available as a research chemical from several scientific supply houses (as were mescaline and LSD) and was sold inexpensively under its chemical name. A few experimental trials with the pure optical isomers show a consistency with all the other psychedelic compounds that have been studied in their separated forms, the higher potency with the "R" isomer. The less potent "S" isomer seemed to be more peaceful and MDMA-like at lower doses, but there were worrisome toxic signs at higher levels. The structure of MDA can be viewed as an aromatic ring (the 3,4-methylenedioxyphenyl ring) with a three carbon chain sticking out from it. The amine group is on the second of the three carbon atoms. The isomers, with the amine function moved to the first of these carbons atoms (a benzylamine) and with the amine function moved to the third (furthest out atom) of these carbon atoms (a (n)-propylamine), are known and both have been assayed. The benzylamine counterpart (as if one were to move the amine function from the beta-carbon to the alpha-carbon of the three carbon chain of the amphetamine molecule) is alpha-ethyl-3,4-methylenedioxybenzylamine or 1-amino-1-(3,4-methylenedioxyphenyl)propane, ALPHA. The hydrochloride salt has a mp of 199-201 °C. At low threshold levels (10 milligram area) there were eyes-closed "dreams" with some body tingling. The compound was not anorexic at any dose (up to 140 milligrams) and was reported to produce a pleasant, positive feeling. It is very short-lived (about 3 hours). The N-methyl homologue is alpha-ethyl-N-methyl-3,4-methylenedioxybenzylamine or 1-methylamino-1-(3,4-methylenedioxy-phenyl)propane, M-ALPHA. It is similar in action, but is perhaps twice as potent (a plus one or plus two dose is 60 milligrams) and of twice the duration. The (n)-propylamine counterpart (as if one were to move the amine function the other direction, from the beta-carbon to the gamma-carbon of the three carbon chain of the amphetamine molecule) is gamma-3,4-methylenedioxyphenylpropylamine or 1-amino-3-(3,4-methylenedioxyphenyl)propane, GAMMA. The hydrochloride salt has a mp of 204-205 °C. At oral levels of 200 milligrams there was some physical ill-at-ease, possible time distortion, and a feeling of being keenly aware of one's surroundings. The duration of effects was 4 hrs. The phenethylamine that corresponds to MDA (removing the alpha-methyl group) is 3,4-methylenedioxyphenethylamine, or homopiperonylamine, or MDPEA, or simply H in the vocabulary of the Muni-Metro world. This compound is an entry in its own rights. The adding of another carbon atom to the alpha-methyl group of MDA gives compound J, and leads to the rest of the Muni-Metro series (K, L etc). All of this is explained under METHYL-J. The bending of this alpha-methyl group back to the aromatic ring gives an aminoindane, and with J one gets an aminotetralin. Both compounds react in animal discrimination studies identically to MDMA, and they appear to be free of neurochemical toxicity. The two possible homologues, with either one or two methyl groups on the methylene carbon of the methylenedioxy group of MDA, are also known. The ethylidene compound (the acetaldehyde addition to the catechol group) has been encoded as EDA, and the acetone (isopropylidine addition to the catechol group) is called IDA. In animal discrimination studies, and in in vitro neurotransmitter studies, they both seem to be of decreased potency. EDA is down two to three-fold from MDA, and IDA is down by a factor of two to three-fold again. Human trials of up to 150 milligrams of the hydrochloride salt of EDA producd at best a threshold light-headedness. IDA remains untested as of the present time. The homologue of MDA (actually of MDMA) with the added carbon atom in, rather than on, the methylenedioxy ring, is a separate entry; see MDMC. A final isomer to be mentioned is a positional isomer. The 3,4-methylene-dioxy group could be at the 2,3-position of the amphetamine skeleton, giving 2,3-methylenedioxyamphetamine, or ORTHO-MDA. It appears to be a stimulant rather than another MDA. At 50 milligrams, one person was awake and alert all night, but reported no MDA-like effects. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

I apologize for my reply. That wasn't called for from me. The people that jump down my throat are correct in doing so. I am not going to blame them or start any drama. Andy was providing information that could be useful and could quite possibly same someones life. All I ask is that everyone please accept my apology. ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....

i dont even do drugs anymore. havent touched anything in a month ------------------ ~*P*L*U*R*~ Four Simple Words To Live By....