1 Journal of Ethnopharmacology 75 (2001) Should we be concerned about herbal remedies Memory Elvin-Lewis Department of Biology, Washington Uni ersity, Box 1137, St. Louis, MO , USA Received 24 November 2000; received in revised form 5 December 2000; accepted 5 December 2000 Abstract During the latter part of this century the practice of herbalism has become mainstream throughout the world. This is due in part to the recognition of the value of traditional medical systems, particularly of Asian origin, and the identification of medicinal plants from indigenous pharmacopeias that have been shown to have significant healing power, either in their natural state or as the source of new pharmaceuticals. Generally these formulations are considered moderate in efficacy and thus less toxic than most pharmaceutical agents. In the Western world, in particular, the developing concept that natural is better than chemical or synthetic has led to the evolution of Neo-Western herbalism that is the basis of an ever expanding industry. In the US, often guised as food, or food supplements, known as nutriceuticals, these formulations are readily available for those that wish to self-medicate. Within this system, in particular, are plants that lack ethnomedical verification of efficacy or safety. Unfortunately there is no universal regulatory system in place that insures that any of these plant remedies are what they say they are, do what is claimed, or most importantly are safe. Data will be presented in this context, outlining how adulteration, inappropriate formulation, or lack of understanding of plant and drug interactions have led to adverse reactions that are sometimes life-threatening or lethal Elsevier Science Ireland Ltd. All rights reserved. Keywords: Herbal remedies; Evolving pharmacopeias; Surveillance and research databases; Adverse effects; Regulatory challenges 1. Introduction During the latter part of the 20th century herbalism has become mainstream worldwide. This is due in part to the recognition of the value of traditional and indigenous pharmacopeias, the incorporation of some derived from these sources into pharmaceuticals (DeSmet et al., 1992a; DeSmet, 1997; Winslow and Kroll, 1998), the need to make health care affordable for all, and the perception that natural remedies are somehow safer and more efficacious than remedies that are pharmaceutically derived (Bateman et al., 1998; Murphy, 1999). For a variety of reasons more individuals are nowadays preferring to take personal control over their health, not only in the prevention of diseases but also to treat them. This is particularly true for a wide variety of chronic or incurable diseases (cancer, diabetes, arthritis) or acute illnesses readily treated at home (common cold etc.) (Kincheloe, 1997). In this respect many individuals have become disenchanted with the address: (M. Elvin-Lewis). worth of allopathic treatments, and the adverse effects that can be anticipated. They are seemingly unaware of the potential problems associated with herbal use or the fact that their limited diagnostic skills, or of those prescribing treatment for them, may prevent the detection of serious underlying conditions like malignancies (Saxe, 1987; Youngkin and Israel, 1996; Donaldson, 1998; Winslow and Kroll, 1998; Shaw et al., 1999; Stewart et al., 1999). Most allopathic practitioners have traditionally considered herbal treatments to be innocuous or alternately, potentially problematical. Three decades ago only a few had any appreciation of the number of remedies that had their origins in herbal medicine and most had a vague impression of what herbalism, or other forms of alternate medicinal practices implied (Lipp, 1996). There was still a great deal of carry-over from the beginning of the 20th century when the introduction of wire services allowed for the dissemination of adverse effects of snake-root concoctions and the like. As early as 1906, misbranding and adulteration were disallowed in the US Herbal remedies, not a part of The Dispensatory of the United States of America, /01/$ - see front matter 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S (00)
2 142 M. El in-lewis / Journal of Ethnopharmacology 75 (2001) were shunned as if the danger associated with one remedy was common to all much like the notion that if one mushroom is poisonous, all must be and by 1938, safety testing was mandated under the Federal Food, Drug and Cosmetic Act. By mid-century, pharmacognosy (study of plants affecting health) was a dying science. Dicta of the day, as outlined in a 1962 law (Kefauver Harris Drug Amendments) required proof of safety and efficacy. This policy determined that only chemically defined and clinically evaluated medicines had value, and if pharmaceutically derived, must be prescribed by allopathic physicians. (Murphy, 1999). Licensure to practice in the US was confined to allopathic clinicians and others in naturopathy and homeopathy whose traditional use of herbs was well defined. Some leeway was also given to practicing traditional healers within Asian and indigenous communities. On the whole, other types of herbalists were not recognized (O Hara et al., 1998). Such was the case for decades, until the age of Aquarius arrived, and the return to nature was the driving force of every flower child. In this wake, self-medication became the rule as old European herbals and indigenous remedies were revisited, and were used with impunity, without concern for adverse effects. In addition, hallucinogens, particularly from American indigenous cultures, became popular as many trying to escape the reality of a war-torn and hidebound world, experimented with altered states. Soon health food stores appeared, specializing in unrefined food, organic-grown vegetables, herbs and herbal preparations. With the opening up of Asian markets, other types of medicines were introduced, and were permitted since they were considered already culturally acceptable. A synthesis of all these types of herbal medicinal practices evolved into what can be called, Neo-Western herbalism. Formulae found in this system are based upon both ethnomedical worth or are simply serendipitous inventions of the formulator. A belief of benefit over single-ingredient drugs is the corner stone of this form of herbalism that subscribes to the notion that primary active ingredients in herbs are synergized by secondary compounds, and secondary compounds mitigate the side effects caused by primary active ingredients (McPartland and Pruitt, 1999). Since it is possible for single taxa to contain a family of related bioreactive compounds varying in potency, it is logical to presume that one or more of these will contribute to the totality of the effects observed (Lewis and Elvin-Lewis 1994; Elvin-Lewis and Lewis, 1995). It would follow that when mixtures of several crude extracts are used in formulations, enhancement of beneficial effects (or greater toxicity) is expected through either synergistic amplification or diminishment of possible adverse side effects. It is also presumed that their combination could prevent the gradual decline in efficacy that is frequently observed when single drugs are given over long periods of time (Borchers et al., 1997). Nowadays such remedies can be still found in ethnic and health food stores, but are also available in pharmacies and grocery stores. Unfortunately there is no universal regulatory system that ensures that these remedies are what they say they are, do what is claimed, or most importantly, are safe (Angell and Kassirer, 1998; DeSmet, 1993; DeSmet et al., 1997). 2. Evolving pharmacopeias 2.1. Major types of herbal medicine Four general types of Herbal Medicine exist which are Asian, European, Indigenous and Neo-Western. Many like the Asian and European systems go back thousands of years, appear in pharmacopeia, and with such a tradition of use are better understood than those of indigenous origins that are often only orally or secondarily recorded (DeSmet et al., 1992a; DeSmet, 1992b) Indigenous herbalism Indigenous medicinal systems are the most diverse and are still practiced where such cultures are intact, but are continuously evolving as contact with other cultures continues. The knowledge may reside exclusively with traditional healers, or be generally known. Information regarding parameters of efficacy and toxicity can vary since claims are primarily anecdotal. Usually regional variations to formulae exist, and plants selected can be quite specific, generic, or inadvertently adulterated. It usually follows that when a remedy is widespread in acceptance its efficacy and safety has a sound therapeutic basis. It is these plants, in particular, that can be found in Neo-Western herbalism Asian medicinal systems The most established types of herbalism are those of Asian origin, particularly from India (Aryuvedic, Unani, Siddha), China (Wu-Hsing) and Japan (Kampo), and today they still follow the ideas of diagnosis and treatment known for millennia (Kanba et al., 1998; Wong et al., 1998; Vogel, 1991). Most of the remedies are mixtures of plants, sometimes also containing animal parts and minerals and are formulated to achieve expected therapeutic goals. They are often referred to as drugs. In these remedies it is not unusual to find more than one plant whose components have complementary effects that seemingly work together to enhance the therapeutic value or other properties of the mixture. This is also true for Indian dental
3 M. El in-lewis / Journal of Ethnopharmacology 75 (2001) preparations that follow traditional formulations (Elvin-Lewis, 1987, 1989). Under ideal conditions, care is taken by traditionally trained practitioners to carefully identify the ingredients, to harvest the plants at very specific times to insure appropriate levels of bioreactivity, to prepare the remedies under strict rules, and to prescribe them to achieve an appropriate clinical response. In spite of the fact that parameters of use may be known to the practitioner, including side effects that can be expected, packaging inserts accompanying commercial products rarely cite these nor do they always accurately represent the contents. Also, there is a general acceptance in Asian countries, particularly India, for patients to seek concurrent treatment through more than one Indian Medicinal System as well as allopathy, or in Chinese herbalism to fraudulently incorporate pharmaceuticals in some remedies. This only compounds issues related to recognizing the source of potential side effects, and it is uncommon for them to be reported at all. Moreover, without enforceable regulatory systems to govern the activities of practitioners and formulators, unexpected adverse reactions are always likely. In this respect, formulations may be inappropriately made, prescribed, or taken. Formulation diversity, due to advertent substitutions, can also exist in preparations with the same name. These changes are not always obvious. Examples can be found in Aryuvedic preparations formulated in southern India, where traditional Himalayan plants are unavailable. Without appropriate prescription labeling, adulterations are a particular problem in Asian medicines, and formulations have been found to contain substitutions of plant ingredients, dangerous levels of toxic plant components, unapproved ingredients like pharmaceuticals and heavy metals in addition to other toxic and allergenic substances (Anonymous, 1989; Chan et al., 1993; Chan, 1997; Drew and Myers, 1997; Ernst, 1997; Ko, 1998). For example, although strictly not herbal remedies, lead has been found in a Laotian preparation known as Pay-loo-ah, a Korean remedy, hai ge fen, containing clam shell powder (Borins, 1998) and in Indian traditional cosmetics used as eyeliners (surma) (Shaw et al., 1997). Chinese herbal medicines are typically unpalatable and can induce nausea and vomiting. Most reported adverse effects on the heart have been associated with Aconitum poisonings and certain topical skin preparations that can also cause liver damage (Chan, 1997; Drew and Myers, 1997; Ko, 1998; Armstrong and Ernst, 1999). In addition, pain or asthma remedies containing Datura metel are recognized to cause anticholinergic effects leading to reduced visceral activity. Liquorice, by affecting the sodium/potassium balance, can cause water retention. More serious are conditions like jaundice and brain damage due to neonatal remedies containing berberine, additive or toxic effects due to undeclared pharmaceuticals like mefenamic acid and diazepam (Gertner et al., 1995), heavy metal adulterations (Schaumburg and Berger, 1992; Kew et al., 1993; Sheerin et al., 1994), or when inadvertent adulterations with Podophyllum emodi instead of londancao (Gentiana spp.) have elicited severe lifethreatening events (Chan, 1997; Drew and Myers, 1997). Highly concentrated alkaloid preparations like tetrahydropalmatine, a potent neuroreactive, can be found in Jin Bu Huan. This Chinese patent medicine used as a painkiller, has been associated with serious adverse reactions episodes in children and adults. Symptoms occurring in long-term users range from acute toxicity, lethargy, muscle weakness, respiratory compromise, bradycardia and coma, to extreme fatigue, fever, jaundice and hepatitis. These events were reported in the Communicable Disease Center s Morbidity and Mortality Weekly Reports (Anonymous, 1993a,b), and by Horowitz et al. (1996). Ginseng preparations imported from China must always be suspect since not only can the content of the ginsenosides vary (Consumer Reports, 1995), but commercial formulations can be adulterated with potent and dangerous plants like mandrake (Mandrogora officinarum) containing scopolamine and Rauwolfia serpentina containing reserpine and stimulants like caffeine from Cola spp. (Drew and Myers, 1997). Certain Chinese remedies may be named the same but are formulated differently depending upon the unique condition of the patient; such is the case with Chinese herbal preparations called Eternal Life. Without appropriate labeling of its ingredients it is almost impossible to identify the source of any adverse effects associated with its use (Sanders et al., 1995) European herbalism European Traditional Medicine has its roots mostly in antiquated Mediterranean civilizations and has over the centuries evolved in its utilization of both European and plants from abroad. In the Middle Ages the color or shape of a plant denoted a cosmic clue to its medical usefulness, and hence the Doctrine of Signatures was a criterion by which many plants were selected, e.g. heart-shaped leaf as a heart remedy, yellow plant parts for treating hepatitis, etc. By the 19th century, some of these medicinal plants had become part of the pharmacopeias of allopathy, naturopathy and homeopathy, and their therapeutic basis investigated by medicinal chemists and pharmacognosists. Usually when compounds are isolated, and sometimes totally synthesized, their pharmaceutical uses are more carefully regulated; aspirin, of course, being an early exception (DeSmet, 1993; DeSmet et al., 1997).
4 Neo-Western herbalism M. El in-lewis / Journal of Ethnopharmacology 75 (2001) Regulatory challenges In its totality European Traditional Medicine has matured along with American herbal introductions into Neo-Western herbalism. In this system single plant preparations that have been either selected from formulations found in ancient pharmacopeias or derived from medicinal plants valued in other cultures, including those of indigenous origin, are sold alone or as mixtures in an assortment of combinations. For example, one of the most popular plants in use in Europe today is Echinacea with its origins in North American (Midwestern) indigenous medicine (Lewis and Elvin-Lewis, 1977). Also, novel formulations can be devised without ethnomedical data to support their merit, or represent a mixture of plants known to a variety of medicinal systems (DeSmet, 1995a). To promote the sale of a particular product, examples exist where supporting ethnomedical data are purposely vague, obtuse, or contrived. While such mixtures may potentiate a remedy s medicinal value, it is also possible that these combinations could promote adverse effects not known when individual plant components are used. Without traditional parameters to guide the consumer, the benefits or risks to these newly contrived formulations are currently unknown. While most British, European and Asian herbalists are formally trained within the context of known pharmacopeias or curricula, American herbalists can vary in their instruction, some being self-taught, while others undertake training in various types of apprenticeship programs. However, like allopathic clinicians, both naturopathic and homeopathic clinicians undergo classical training and in the US and Canada some schools of naturopathy also teach homeopathy as a sub-specialty. Both of these disciplines utilize specifically formulated medications that are understood for parameters of use. However, philosophies of diagnosis and treatment differ. Naturopathy, based on hydrotherapy and dietary treatment, currently prescribes formulations containing plant extracts or phytochemicals at pharmacognostically determined levels of efficacy. The philosophy of treatment is two-fold and includes both curative and maintenance (normalization) aspects. Homeopathic formulations (that contain plant extracts and other substances) are compounded under the philosophy that substances that cause specific toxic effects can, at extremely dilute concentrations, reduce similar effects elicited by disease states. While homeopathic remedies are often considered to only elicit placebo-like actions, practitioners recognize their worth, and understand that these remedies are not only bioreactive but may also elicit minor adverse effects like rashes, nausea, vomiting, agitation, shaking and allergic reactions (Shaw et al., 1997; Glisson et al., 1999) Asia Overall, the incidence of serious adverse reactions is significantly lower with most of these therapeutic remedies when compared to pharmaceutically derived drugs. However, the need still exists to more closely monitor practitioners and formulators of any traditional medicine, including those of Asian origin, so that medicinal irregularities and unethical practices are reduced. Also, Chinese herbal prescriptions are individualized and when dispensed are not usually labeled, and should adverse effects arise, identification of their contents is difficult unless the patient has been provided a written copy of the formulation. Presuming that the formulation contains the plants described, verification may be impossible after processing has occurred. Should traditional remedies be prepared in an Asian country, and imported, the task of insuring safety is even more difficult since the notion of incorporating potentially toxic herbs or heavy metals may not be considered harmful in the country of origin (Natori, 1980; Anonymous, 1989; Shaw et al., 1997) Europe Unfortunately, regulatory standards vary from country to country, and thus claims of content, efficacy, and safety of any herbal remedy cannot always be assured. Germany is the leader in evolving rational regulatory policies (Benzi and Ceci, 1997). There, plant remedies are carefully delineated and registered in Commission E Monographs with known risk/benefit/drug interactions cited, and consistency of bioreactive compounds chemically defined as phytopharmaceuticals (Blumenthal et al., 1998). More detail is provided in the 50 monographs published by the European Scientific Cooperative on Phytotherapy and 10 additional monographs are underway (Blumenthal, 1999). While self-medication is the norm, prescriptions for some medications are also mandated. Most European countries are evolving similar policies (Benzi and Ceci, 1997), although in the United Kingdom only some herbal preparations fall under such strict regulatory guidelines (Mills, 1995) US In the US regulatory mechanisms regarding herbalism were non-existent until only a few years ago, and even then and now they still lack true enforcement capability. FDA Commissioner Kessler voiced concerns regarding safety in 1993 and proposed removal of herbal products without proven safety and efficacy. As a reaction to this proposal the Dietary Supplement Health and Education Act (DSHEA) was inaugurated
5 M. El in-lewis / Journal of Ethnopharmacology 75 (2001) in Under this act many botanical medicines defined as a vitamin, a mineral, an herb or other botanical (or) amino acid are now sold under the guise of food or dietary supplement (Brevoort, 1998; Murphy, 1999). As long as no medical claims are present on the label they are exempt from strict pharmaceutical regulations. Any display literature must further claim that the product has not been reviewed by the FDA or is not intended for medication. Also in 1997, a Federal Commission on Dietary Supplements was established that recommended that manufacturers provide sciencebase evidence to consumers. To some physicians like Angell and Kassirer (1998), these guidelines, and vague or oblique claims related to the maintenance of good health, still begs the issue regarding proven safety or efficacy. They emphasize that since these herbal remedies are not classified as medications they are not under FDA scrutiny. Without being appropriately evaluated for content, safety or efficacy it is difficult to determine parameters of use. However, should adverse reactions become apparent, the FDA could investigate and intervene to remove the product (Murphy, 1999). Moreover, the FTC (Federal Trade Commission) is active in defining the regulatory framework for advertising claims for dietary supplements. The legal and regulatory aspects of these US government agencies in overseeing the herb and dietary supplement industry from the perspective of the Consumer Healthcare Products Association has been recently reviewed and is a useful reference to those requiring details of such aspects (Soller, 2000). Attempts are being made to bring some sense out of this current regulatory chaos since it is in the best interest of everyone to do so. In this regard, pharmacognosists and natural products chemists have once again become active in trying to understand the therapeutic basis of herbal remedies and toxicologists are addressing issues of the origins of potential adverse effects as incidences of associated use or abuse become evident. As a complement to these efforts a number of organizations are preparing monographs to delineate details of herbs that are popularly used as phytomedicines and medicinal plant preparations so that their recognition as official medicines may result (McGuffin et al., 1997). The most ambitious is that of the American Herbal Pharmacopeia and Therapeutic Compendium with plans to publish at least 2000 monographs of this nature. Also, the herb trade in recognizing its responsibility to provide appropriate guidelines, has recently published through the American Products Herbal Association (AHPA) The Botanical Safety Handbook, 2nd edition (1998). The FDA accepts this organization s Herbs of Commerce as the authoritative text for label nomenclature related to available herbal products. To aid pharmacists in understanding risks and benefits of herbal products, the United States Pharmacopeia (USP) is also compiling standard monographs for herbal dietary supplements and dispensatory information (DI). They have already published 11 monographs and an additional 12 are under preparation. In order to set standards to document the quality of herbal products, and outline the therapeutic parameters for safe and effective use, publication of the WHO Monographs on Selected Medicinal Plants is on-going (Akerele, 1993). Volume 1 (1999) contains 28 monographs on 31 plant species and Volume 2 to be published in 2000, an additional 29 monographs (Blumenthal, 1999). Furthermore, the FDA is considering reviewing certain botanicals via the IND/NDA (Investigational New Drug/New Drug Application) process. Presently there are at least 50 botanicals or botanical formulas holding active IND applications. Priority will be given to those with a long-history of safety, particularly for short-term use since information is unlikely to be adequate to support claims of safety for long-term use. In some cases issues related to accompanying chemistry and toxicological data remain to be resolved (Murphy, 1999). Recently, a Federal Commission on Dietary Supplements has been established (1997) recommends that manufacturers provide science-based evidence to consumers. Also to support evaluation of herbal medicines and other non-traditional remedies the National Institutes of Health (Bethesda, MD) formed the Office of Alternative Medicine in 1992 that has recently been up-graded to the National Center for Complementary and Alternative Medicine (Murphy, 1999). Eventually, these initiatives and others evolving elsewhere, are expected to provide needed information to validate this type of therapy. To aid in this endeavor two searchable databases generated by the US National Institutes of Health on dietary supplements exist. The International Bibliographic Information on Dietary Supplements (IBIDS) can be accessed at the ODS website odp.od.nih.gov/ods. Currently, IBIDS contains citations and abstracts of published international, scientific literature on dietary supplements, including vitamins, minerals, and botanicals and is updated quarterly. Scheduled to go online in 2001, CARDS (Computer Access to Research on Dietary Supplements) will identify ongoing, federally funded research on dietary supplements and individual nutrients (CAM, 2000). Within this context clinical evaluation protocols should include those outlined in Table Canada In Canada similar regulatory mechanisms are being instituted and in March of 1999, an Office of Natural Health Products was created to assure that Canadian consumers have access to a full range of safe health products. The Office will undertake or coordinate all the regulatory functions within the life-cycle of natural
6 146 M. El in-lewis / Journal of Ethnopharmacology 75 (2001) health products from pre-market assessment for product licensing through licensing of establishments, post-approval monitoring and the compliance and enforcement tools appropriate with ensuring health protection. This will include the development of appropriate training standards of manufacturing and distribution establishments. Within this context, criteria to determine the applicability of efficacy as reflected in labeling claims will be established and information disseminated to allow the Canadian consumer to make informed self-care decisions. Accommodations will be made for aboriginal healers. Currently, Health Canada policy allows an individual to import a 3 month supply of a drug product for their own personal use that is not subject to these evolving regulatory policies (Koryrskyj, 1977). 4. Surveillance of adverse effects through databases Regardless of the type of herbalism being practiced some adverse reactions are more easily recognizable than others. Postulates have been proposed by Hughes (1995) to define if adverse effects are linked to a drug use. According to Stewart (1990), DeSmet (1995b), events that are pharmacologically predictable are often dose-dependant and thus preventable by dose reduction, or if allergenic, by elimination. However, in spite of the mode of application, individual differences in physiology may elicit a variety of idiosyncratic local or systemic reactions, including those that are life threatening. Age may also be a factor and those remedies most frequently used by the elderly may elicit varying responses (Ernst, 1999). Similarly, long-term use can produce predictable reactions or consist of delayed effects such as carcinogenicity and teratogenicity. To better understand the scope of these problems and bring them forward to the public DeSmet (1995b) Table 1 Proposed clinical evaluation protocol for the development of an herbal drug Confirm ethnomedical value in country of origin Note all parameters of use particularly among children, the aged or others with underlying disease states Review traditional formulations to understand rationale of use Know variations to standard formulations and reasons for additions or substitutions Conduct controlled clinical trial with formulation considered to be the best Identify bioreactive components to insure standardization of content Conduct toxicological studies to understand safe parameters of use Conduct placebo-based clinical trials following appropriate guidelines for patient entry, evaluations of efficacy etc. to comply with regulations where product is to be sold proposed that forms of herbal post marketing surveillances be conducted to detect serious adverse reactions, quantify their incidence and identify contributive and modifying factors. Obviously, the success of such endeavors depends on those willing to voluntarily and spontaneously report such events to appropriate health care officials, pharmocologists (http,//www.faseb.org/ aspet/h&mig3.htm ctop), regulatory bodies (FDA MEDWATCH (http,//www.vmcfscan.fda.gov/ dms/ aems.html)), and responsible parties in the herb trade industry itself, like the American Botanical Council (http,//www.herbs.org), who are collating these data for public dissemination (Winslow and Kroll, 1998). With the number of mixed plant formulations now marketed in the US alone, it is particularly important to refer to web sites that can provide on an on-going basis useful information on current adverse reactions. Overall, the US is still a long way from the development of standardized herbal drugs, called phytopharmaceuticals, which have been formulated (in a fashion) to ensure a reproducible effect by undergoing suitable means of identification and clinical evaluations to achieve international approval. Obviously these are needed steps if allopathic acceptance is to follow (Angell and Kassirer, 1998). In the interim, information is accumulating that is providing appropriate ways to understand herbal therapies and can be elicited from internet sources like the National Center for Complementary and Alternative Medicine (http,//nccam.nih.gov), American Botanical Council (www.herbalgram.org), US Food and Drug Administration (www.fda.gov), and the US Pharmacopeia (www.u.s.p.org) (Murphy, 1999). 5. Bridging the gap between herbalism and allopathy Most importantly, it is now recognized that allopathic clinicians have little training in understanding how various forms of herbalism and self-medications are impacting on the health of their patients, who are often, also under prescriptive medication. However, as awareness of potential interactions with allopathic treatments and herbal remedies increases, many clinicians and hospitals are eliciting this information on admission questionnaires (Murphy, 1999). To ensure that patients will be forthcoming with the information, it is recommended that such solicitations be carefully worded so as not to be judgmental. This is essential since a patient s response to treatment, particularly in a clinical trial, could be distorted when concurrent uses with herbal remedies are not revealed (Kassler et al., 1991; Buchness, 1998; Donaldson, 1998). To increase the sensitivity of future practitioners, a number of US medical schools are developing courses in Complementary and Alternative Medicine, including