[TAC] Ethnobotanicals

Table of Contents

  • Introduction
  • History and Traditional Uses
  • Medicinal Uses and Current Research

  • Changes in Usage
  • Future Research

  • Regulation

  • Conclusions

  • Citations
  • Introduction

    Ephedra sinica, also known as Ma Huang, is a powerful stimulant with a long tradition of use by Chinese and Mongolian peoples (Chevallier, 1996). It has been used for a variety of medicinal uses from treating colds, asthma and hayfever to various kidney ailments (Chevallier, 1996). One of the compounds isolated from Ephedra, pseudoephedrine, is currently used in many pharmaceutical decongestants and antiasthmatic medicines, and various herbal preparations are currently used as stimulants and weight loss aids. In recent years, Ephedra preparations, often containing caffeine, have been marketed as producing effects similiar to 'Ecstasy' an amphetamine (MDMA) based recreational drug (Blumenthal and King, 1997; Saunders, 1997).There have been serious and even fatal side effects to large doses of these Ephedra drugs because of their cardiac effects. For these reasons the U.S. Food and Drug Administration is now considering new regulations on the import and use of Ephedra sinica (Blumenthal and King, 1997).

    This paper explores these issues surrounding Ephedra by discussing the plant's biology, medicinal history of the plant, its pharmacological properties, current uses and research. Historical and current uses are compared and issues recommendations regarding regulation are offered.

    History and Traditional Uses

    Ephedra sinica is an evergreen shrub that is native to northern China and inner Mongolia. In Chinese, it is called "ma huang". It has been called the world's oldest medicine, since it has been used in traditional Chinese medicine for over 5,000 years (Castleman 1995). Ephedra sinica grows to about 20 inches in height, has long narrow stems, and small leaves that are reduced to scales at the nodes. Stamens and pistils are on separate flowers, and seeds are enclosed in cones (Grieve, 1971). It is propagated from seed in the fall, or by root division in spring or fall. It grows primarily in desert areas, and requires dry soil (Chevallier, 1996). Harvesting of the stems for medicinal use is done in the fall, before the first frost, because late gathering improves the efficacy of the drug (Taylor, 1965). Related species grow in North America and India, but have slightly different chemical compositions, and, therefore, different medicinal properties (Chevallier, 1996). For example, Ephedra antisyphilitica is native to North America, and was introduced by Native Americans to Mormon settlers, who believed that its tea ("Mormon tea" or "whorehouse tea") prevented syphilis (Taylor, 1965).

    While Ephedra is known to have been used in Chinese medicine for at least five centuries, it may have been used long before that time, since it was also found in a 60,000 year old burial site in Iraq, along with seven other medicinal plants (Chevallier, 1996). "The origins of Chinese medicine are lost in legend, but authorities agree that Chinese physicians began prescribing Ephedra tea for colds, asthma and hayfever around 3,000 BC," (Castleman, 1995).

    The first written account of Ephedra sinica's use is recorded in the Pen Ts'ao of Shen Nung, a Chinese herbalist. This was written in 2800 BC, and lists 366 plant drugs, including Ephedra sinica (Griggs, 1982). It is possible that ancient Greeks had knowledge of Ephedra and its medicinal properties. An ancient Roman writer named Pliny described a plant called "ephedron" used by the Greeks:

    "The Greeks hold various views about this plant...assuring us that so wonderful is its nature, its mere touch staunches a patient's bleeding...its juice kept in the nostrils checks hemorrhage... and taken in sweet wine, it cures cough... Ephedron... has no leaves, but numerous rush-like, jointed tufts...For coughs, asthma, and colic, it is given pounded in dark-red wine" (Schultes and von Reis, 1995).

    It is surprising that the medicinal properties of curing cough, and stopping hemorrhaging are associated with a plant called "ephedron", since these medicinal properties are associated with ephedrine. Similar descriptions of ephedron are found in the writings of Dioscordes. It is unknown whether the Greeks obtained this information of Ephedra from the Chinese, or discovered it themselves. There is no known record of travel between China and Greece or Rome in antiquity (Schultes and von Reis, 1995).

    The Chinese traditionally used the dried stems crushed, in powder form, or in a tea. It was used to "disperse cold, help problems caused by external cold, and aid movement of lung qi," (Chevallier, 1996). Qi is a word used in Chinese traditional medicine that means human vitality . In addition, it was used by Zen monks to "promote calm concentration during meditation. And, according to legend, bodyguards of Ghengis Khan, threatened with beheading if they fell asleep on sentry duty, used to take a tea containing Ephedra to stay alert," (Chevallier, 1996).

    Ephedrine, the active alkaloid in Ephedra sinica, was first isolated, and characterized by a Japanese chemist, N.M. Nagai in 1887. However, his work was not recognized by the West, until, in 1924, K.K. Chen and C.F. Schmidt, of the Peking Union Medical College began to publish a series of papers on the pharmacological properties of ephedrine (Tyler, 1994). Soon after, the Eli Lily company began marketing ephedrine to the West as a therapy for asthma, and a stimulant to the central nervous system, (Griggs, 1982). Thus, Ephedra was the first Chinese herbal remedy to yield an active constituent, ephedrine, that was later widely used in Western medicine (Tyler, 1994). In 1927, ephedrine was admitted as a standard drug by the American Medical Association, and it was synthesized in the laboratory. However, the demand for ephedrine was so high that not all of the needed drug could be synthesized. So, large amounts of Ephedra sinica were imported from China. In fact, in 1940, nearly 1.5 million pounds were imported. With the adoption of the Communist regime in China (1949), importation of Ephedra sinica to the United States was stopped, and so the U.S. turned to importation from India and Pakistan, as well as to cultivation of the plant in the U.S. (Taylor, 1965). In the 1950's the pronounced side effects of ephedrine, namely increased blood pressure and heart palpitations, led the pharmaceutical companies to largely switch to pseudoephedrine, a close analog (Vitawise, 1997).

    Medicinal Uses and Current Research

    The leaves and stems of Ephedra sinica contain many potentially active compounds such as tannins, saponin, falvone, and volatile oils, but it is the protoalkaloids (ephedrine, pseudoephedrine, norpseudoephedrine) which have been isolated and used for their particular medical properties as asthma and cough medications (Chevallier, 1996).

    Table I. Key Compounds Isolated from Ephedra sinica

    Ephedrine - A water-soluble salt of an alkaloid.*

    Pseudoephedrine - An analog of ephedrine.*

    Norpseudoephedrine - An analog of ephedrine.* (Amlodipine)

    * (Vitawise, 1997)

    Current herbal uses of Ephedra in China are very similar to what they have been historically. It is often taken to relieve chills, fevers, coughs and wheezing, and also is taken in powder form in combination with Rehmannia (Rhemannia glutinosa) to treat kidney yin deficiency (Chevallier, 1996). Ephedra is currently used as herbal medicine in Western countries in a decoction for asthma, hay fever, acute onset of colds/flu, to raise blood pressure, and possibly to initiate menstruation (Chevallier, 1996). Also it is used in tincture form to alleviate rheumatism and for aches and pains (Chevallier, 1996). Also used in combination with Lobelia, Orindelia and Symplocarpus for asthma; with Echinacea and Uliginosum for hay fever; with Equisetum in enuresis.

    Today, many over-the-counter cough suppressant, antiasthmatic and decongestant medications contain pseudoephedrine (Zurich, 1993). Most Americans are probably familiar with brands names such as Actifed, Comtrex, Dristan, Sudafed which all contain pseudoephedrine salts, generally either pseudoephedrine hydrochloride or sulfate (Zurich, 1993). The hydrochloride salt is more common (Zurich, 1993). Pseudoephedrine works by stimulating the nerve fibers of the sympathetic nervous system. It produces a narrowing of the blood vessels of the nasal passages and the sinuses (AVM, 1997). It is often combined with antihistamines or codeine to further reduce nasal secretions and suppress cough (AVM, 1997). Generally these decongestants are ingested as tablets or cough syrups.

    Though most of the pharmaceutical industry switched to pseudoephedrine in the 1950s, ephedrine is still used in some antiathasmatics, again generally in the form of a salt (hydrochloride, sulfate or tannate). Also ephedrine sulfate is used for its vasoconstriction properties as a hemorrhoid suppository (The Herbal Library, 1997; Zurich, 1993). Norpseudoephedrine, also known as amlodipine, is a peripheral arterial vasodilator that reduces blood pressure, and is used to treat angina by reducing the heart's workload (RxList, 1997). The precise mechanisms by which Amlodipine relieves angina have not been fully researched (RxList, 1997), but it is known to be a calcium channel blocker, which effects smooth and cardiac muscle (Zurich, 1993).

    Various herbal preparations containing ephedrine are used as dietary supplements for weight loss, as well as stimulants. Many preparations are currently marketed as legal alternatives to 'Ecstasy'. Ecstasy is an illegal amphetamine which has the effect of releasing serotonin and dopamine in the brain and producing sensory stimulating effects and acting as an aphrodisiac (Saunders, 1997). However the illegal drug contains no extracts from Ephedra. 'Herbal Ecstasy' is one of the several brand names for a preparation of ephedrine and caffeine claimed to have similiar effects despite different biochemical actions. It is reported to have severe side effects, especially in large doses and the FDA is currently considering stricter regulation of it.

    Table II. Medicinal Properties of Ephedra sinica and its constituents

      FORM USES / ACTIONS
    Herb (stems and branches) Decoction, Powder, Tincture Decongestant, opens sinuses** Increases sweating, dilates bronchioles (antiasthmatic use), diuretic, central nervous system stimulant, raises blood pressure, alleviates aches and rheumatism, alleviates hay fever/colds, lowers fecer*
    Ephedrine Tablets, Suppositories Antiallergenic, antiasthmatic, antispasmatic, decongestant, cough suppressant, stimulant, vasoconstrictor.
    Hydrochloride Sulfate Tannate    
    Pseudoephedrine Tablet, liquid Decongestant, cough suppressant
    Hydrochloride Sulfate    
    Norpseudoephedrine Tablet, liquid Peripheral vasodilator used to treat angina
    (Amlodipine)    

    * (Chevallier, 1996) ** (Vitawise, 1996)

    Ephedra and its extracts have been shown to have serious side effects, but general indications are that the herb itself may not have as effects as severe as ephedrine in isolation (Chevallier, 1996). Up to 15 deaths have been attributed to Ma Huang or ephedrine in the U.S. in the last few years (Waxman, 1996).

    Table III. Side effects of Ephedra sinica and its constituents

      FORM SIDE EFFECTS OR CONTRAINDICATIONS
    Herbs (stems and branches) Decoction, Powder, Tincture Not recommended for pregnant woman (due to uterine contractions) or to persons with heart disease, diabetes, glaucoma or an overactive thyroid gland
    Effects include: headaches, tremors, insomnia, dehydration.
    Ephedrine Tablets, Suppositories Not recommended for pregnant or nurshing woman.
    Hydrochloride Sulfate Tannate   Effects include: restlessness, dizziness, palpitations, pressor actions, anxiety, tenseness, tremors, hallucinations, seizures, respitory effects, cardiac failure.
    Pseudoephedrine Tablet, liquid Effects may include: headaches, tremors, insomnia, heart palpitations, nasea, dizziness, dehydration.
    Hydrochloride Sulfate    
    Norpseudoephedrine Tablet, liquid Not recommended for persons with aortic stenosis, pregnant or nursing woman.
    (Amlodipine)    

    * (Chevallier, 1996) ** (Vitawise, 1997) *** (AVM, 1997)

    Current clinical research on extracts from Ephedra include studies on cardiovascular effects, allergic effects, smoking cessation, antiobesity effects, renal toxicity, and even effects on barotitis (problems with pressure changes during scuba diving or airtravel). (See Table IV). With the current concerns about fatalities, more clinical studies of the effects of ephedrine on cardiac irregularities are also being conducted.

    Table IV. Current Clinical Studies of Ephedra sinica and/or Constituents

    Bechgaard, E. 1997. "Reversibility and clinical relevence of
    morophological changes after nasal application of ephedrine nasal drops."
    Intl. J. of Pharmaceutics. 152(1):67.
    Lyon, C.C. and Turney, J.H. 1996. "Pseudoephedrine toxicity in renal
    failure." Brit. Journal of Clin. Pharm. 50(7): 396.
    Norregaard, J. et al. 1996. "The effect of ephedrine plus caffeine on
    smoking and postcessation weight gain." Clinical pharmacology and
    therapeutics. 60(6):679.
    Fuller, M.A. et al. 1996. "Clozapine-Induced Urinary Incontinence:
    Incidence Treatment with Ephedrine." J. of Clin. Psych. 57(1):514.
    Stanley, N. et al. 1996. "Comparison of the effects of
    astemizole/psuedoephtripolidine/ pseudoephedrine on CNS activity and
    psychomotor function." Intl. Clin. Pyschopharm. 11(1):31.
    Bronsky, E et al. 1995. "Comparative efficacy and safety of once-daily
    loratadine- pseudoephedrine combination versus its components alone and
    placebo in the management of seasonal allergic rhinitis." J. of Allergy
    and Clin. Immunology. 96(2):139.
    Shaikh, W.A. 1995. "Ephedrine-saline nasal wash in allergic rhinitis." J.
    of Allergy and Clin. Immunology 95(5):1.
    Pasquali, R. 1993. "Clinical aspects of ephedrine in the treatment of
    obesity." Intl. J. of Obesity. 17 S .

    Cheetham, R.F. et al. 1993. "Astemizole and Pseudoephedrine Combination for the Symptomatic Treatment of the Common Cold and Influenza." Current
    Theropeutic Res. 54(3):358.

    Brown, M. 1992. "Pseudoephedrine for the prevention of barotitis media: a
    controlled clinical trial in underwater drivers." Annals of Emergency Med.
    21(7):849.
    Chua, S. 1991. "Cardiovascular effects of a chloropheniramine/paracetamol
    comibination in hyper- tension patients who were sensitive to the pressure
    effects of pseudoephedrine." Brit. J. of Clin. Pharm. 31(3): 360.


    Changes in Usage, Future Research and Regulation

    Ephedra sinica has been used for thousands of years for its medicinal properties. Just as the Chinese used Ephedra in 3000 BC for the alleviation of cold symptoms, consumers are still using it today for the same reason. Certainly, the traditional uses of the Ephedra sinica plant were important in giving rise to the treatments, based on extracts from the plant, that are in use today.
    In the United States, herbal preparations of the plant have become popular recently, but have led to concerns about its dangerous side effects. The drug is being abused as a mechanism for weight loss, sexual stimulation, and heightened athletic performance. When used improperly, irregular heartbeat, sleeplessness, anxiety, tremors and headaches occur. Some extreme reactions are seizures, heart attacks, and strokes; and approximately 17 deaths have been reported that were blamed on the use of Ephedra-based products. Herbal Ecstasy is a drug, based on ephedrine, which promises euphoria and heightened sexual awareness. A similar drug, called Ultimate Xphoria has been marketed to appeal to a young adults. In 1996, these drugs were readily available at beach shops, night clubs, herb shops and health food stores. Marketing for these drugs has been conducted on the internet as well.
    Several recent fatalities related to Ephedra drugs have increased concerns. In March 1996, a group of college students on spring break in Panama City, Florida, ingested the herbal products. A 20-year old man from NY, Peter Schlendorf, took eight pills, instead of the two to four pills recommended on the Ultimate Xphoria package. He reportedly said he was not feeling well, and his friends left him to rest in the hotel room while they went out on the town for the night. When his friends returned the hotel room, they found Schlendorf dead. The coroner said that Schlendorf's death was due to the ingestion of Ultimate Xphoria (Blumenthal & King, 1997). Another unfortunate case was that of a 35-year old women who used an Ephedra based product as a weight loss alternative. She took pills for only 11 days before dying of a heart attack (Neergaard, 1997). A Boston college student drank an ephedrine-containing 'protein drink' and then died of a heart attack. The coroner stated that the drink had killed portions of his heart tissue (Neergaard, 1997).
    More and more, the risks that go along with the drug are being noted by officials. For example, New York officials have passed legislation requiring Ephedra to be treated as a controlled substance, as are drugs such as morphine, opium and coca leaves. Other states like Connecticut, Tennessee, Nebraska, and Massachusetts have begun putting restrictions on the products containing Ephedra. However some are only requiring a warning label on the products (Swartz, 1997).
    In 1996, the Food and Drug Administration (FDA) made efforts to remove the ephedrine-containing products from the market. But an amendment to the Federal Food, Drug, and Cosmetic Act puts the burden of proof on the FDA; they must prove that each individually marketed product which contains Ephedra is unsafe (Blumenthal & King, 1997).
    Clinical research has become more focused on the possible side effects since the number of deaths rose in 1996. More research on the effects of ephedrine on heart tissue are clearly needed. Current studies show that maintenance of the proper dosage is critically important and that this is the best way to avoid the toxic effects of the herb. As of June 1997, the FDA made plans to ban supplements containing more than eight milligrams of ephedrine. The maximum daily intake should be no more that 24 milligrams (Blumenthal & King, 1997).

    Conclusions

    Based on the information presented in this paper, we believe that Ephedra sinica and any products containing ephedrine extracts of the plant should be regulated. While the plant is a useful medicinal herb, the costs associated with its misuse are high. Ephedrine based products are being marketed as legal alternatives to sexually stimulating recreational drugs, as well as for weight loss and athletic enhancement purposes. But most users are not likely to be aware of its potentially lethal side effects when taken in increased doses. Ephedra and its constituents are being consumed at unsafe levels, and are being mixed with other drugs such as caffeine which may be exacerbating the effects. The seventeen deaths blamed on Ephedra products in last few years suggest strongly that regulation is needed. We believe that products based on Ephedra sinica should be regulated by the FDA as prescription drugs.

    Citations

    AVM. "Pseudoephedrine". http://www.avm.com.au/agtm/drugprofiles /pseudoephedrine.html. Accessed on October 16, 1997.

    Blumenthal, M. and King, P. "The Agony of the Ecstasy." HerbalGram 37, 1997. (pp. 20-49)

    Castleman, Michael. The Healing Herbs: The Ultimate Guide to the Curative Power of Nature's Medicines. New York: Bantam Books, 1995. (pp. 230-231)

    Chevallier, Andrew. The Encyclopedia of Medicinal Plants. New York: DK Publishing Inc., 1996. (pp. 11, 16, 38, 93)

    Grieve, M. A Modern Herbal, Volume I. New York: Dover Publications, 1971. (p. 286)

    Griggs, Barbara. Green Pharmacy: A History of Herbal Medicine. New York: The Viking Press, 1982. (pp. 10, 278-279)

    Neergaard, Lauran. "FDA Proposes Ephedrine Crackdown." http://ww.vais.net/~bhirsch/ephedwp.htm. Associated Press, June 2, 1997.

    RxList. "Psuedoephedrine." http://www.rxlist.com. Accessed October 22, 1997.

    Saunders, Nicholas. "Herbal Ecstasy" http://ecstasy.org/ Accessed October 22, 1997.

    Schultes, R. E., and von Reis, S. Ethnobotany: Evolution of a Discipline. Portland, Oregon: Dioscordes Press, 1995.

    Swartz, John. "FDA: Stifle Herbal Stimulant." The Washington Post, June 3, 1997.

    Taylor, Norman. Plant Drugs that Changed the World. New York: Dodd, Mead & Company, 1965. (pp. 102, 104, 112-113)

    The Herbal Library. "Monograph: Ephedra." http://www.healthlink.com.au/nat_lib/htm-data/htm-herb/bhp620.htm. Accessed October 16, 1997.

    Tyler, Varro E. Herbs of Choice: The Theraputic Use of Phytomedicinals. New York: Pharmaceuutical Products Press, 1994. (pp. 88-89)

    Waxman, Sharon. "Lawsuits Blame Women's Deaths on Unregulated Herbal Products." The Washington Post, March 24, 1996.

    Vitawise. "Ma Huang - aka - Ephedra." http://www.vitawise.com/mahuang.htm. Accessed on October 16, 1997.

    Zurich, Daniel B. Physician's Desk Reference. New Jersey: Medical Economic Company, Inc., 1993. (pp. 307,308,316,768,1210,2042,2503,2532,2535).

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