About Herbs, Botanicals & Other Products

Scientific Name
Ephedra sinica, Ephedra equisetina
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Common Name

Mahuang, herbal ecstasy

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Brand Name

Herbal Ectasy, Herbal fen-phen

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Clinical Summary

Derived from the dried rhizome and root of the plant, ephedra has been used as a medicinal herb for thousands of years in India and China. It is commonly consumed in low doses and in combination with other herbs to promote urination and to treat asthma, bronchitis and coughs.
Ephedrine and pseudoephedrine, the major constituents, are non-selective sympathomimetic agents with both alpha and beta activities and have direct and indirect CNS stimulation effects, which account for the medicinal properties of the herb. Ephedra also has antibacterial and anti-inflammatory properties (1) (2) (3). Ephedra has been widely promoted as a natural stimulant and appetite suppressant. Although limited clinical data support this use, several cases of stroke, myocardial infarction and death in patients with no prior history of vascular disease have been reported (10).

Misuse and overdose of ephedra have resulted in heart attack, stroke, seizure, psychosis and death (8). Drug/herb interactions are major concerns (1) (4) (11) (14). Even a single dose of a weight loss supplement containing ephedra and caffeine increased QTc interval and systolic blood pressure significantly (15). The FDA has banned the sales of dietary supplements that contain ephedra because of their significant risk to human health (12) (13).

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Purported Uses
  • Asthma
  • Bronchitis
  • Common cold
  • Cough
  • Infections
  • Promote urination
  • Strength and stamina
  • Weight loss
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Constituents

Alkaloids: L-ephedrine, D-pseudoephedrine, methylephedrine, D-N-methylpseudoephdrine, and L-norephedrine.
(4) (5)

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Mechanism of Action

The major alkaloids in ephedra, ephedrine and pseudoephedrine, are CNS stimulants. They are non-selective sympathomimetic agents with both alpha and beta activities. These alkaloids can be used as decongestants because they constrict peripheral blood vessels, but in high doses, they also raise blood pressure (1) (2) (3). The CNS stimulation property contributes to ephedra’s appetite suppressant effects and its reputation as a weight loss agent (7). This effect, however, may lead to other cardiovascular adverse reactions such as stroke and heart attack (8). Ephedra’s antiasthmatic effect arises from its ability to relax bronchial smooth muscle. Studies indicate that ephedra also has antibacterial, antiinflammatory and uterine stimulatory activities (9).

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Pharmacokinetics

Ephedra alkaloids are absorbed in the intestine. A small amount is metabolized in the liver but most is excreted in the urine unchanged (9). Excretion rate is adversely affected by the urine pH value. Serum half-life is 3 to 6 hours for ephedrine and 5 to 8 hours for pseudoephedrine (1).

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Warnings

The FDA has banned the sales of ephedra-containing dietary supplements. Consumers are urged not to buy or use these products (12) (13). These products have made unsubstantiated claims and may pose significant health risks (6). Possible adverse effects include hypertension, palpitations, heart attack, stroke, seizures, psychosis and death (10).

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Contraindications

Anxiety, hypertension, heart disease, glaucoma, prostate enlargement, hyperthyroidism.
The safety of ephedra for use during pregnancy has not been established. Since ephedra can stimulate uterine contraction, women who are pregnant should not consume this product (8) (9).

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Adverse Reactions

Reported: Hypertension, palpitations, heart attack, stroke, seizures, insomnia, cardiomyopathy, psychosis and death (6) (10) (14), coronary artery aneurysm and thrombosis (16), and gastric mucosal injury (17).

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Herb-Drug Interactions

Aspirin: May increase risk of cerebral hemorrhage.
Benzodiazepines and other sedatives: Effects may be antagonized by ephedra.
Beta-adrenergic agonists: Ephedra may potentiate effects of beta-adrenergic agonists.
CNS stimulants: May increase stimulatory effects.
(1)
Theophylline: May decrease its effectiveness (18).
Digoxin: Concomitant use can cause arrhythmia (1) (11).
Monoamine-oxidase inhibitors (MAO-I): Concomitant use can cause hypertensive crisis (4).

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Herb Lab Interactions

Consumption of ephedra alkaloids may interfere with urine amphetamine test resulting in false-positive readings.
Ephedra may increase blood glucose levels.
(11)

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Literature Summary and Critique

Boozer C, et al. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord 2001;25:316-24.
Sixty-seven subjects participated in a randomized, double-blind placebo controlled study. They were given supplements containing 72 mg of ephedra and 240 mg of caffeine per day. After eight weeks, subjects from the active treatment group lost an average of 4.0 kg as compared to 0.4 kg in the placebo group. Serum triglyceride and hip circumference were also reduced in the active treatment group. The study concluded that this mixture effectively promoted short-term weight and fat loss. However, adverse symptoms such as dry mouth, insomnia and headache were reported. More studies are needed to explore the long-term effects.

Samenuk D, et al. Adverse cardiovascular events temporally associated with ma huang, an herbal source of ephedrine. Mayo Clin Proc 2002;77:12-6.
Based on the data obtained from the comprehensive database Adverse Reaction Monitoring System of FDA, the authors found 926 cases of possible ephedra toxicity reported between 1995 and 1997. Analysis of 37 cases indicated that ephedra and related products can cause stroke, myocardial infarction and sudden death. These adverse effects are not dose-related and can happen to patients with no prior history of vascular disease.

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References
  1. Barnes J, et al. Herbal Medicines. Second Ed. London: Pharmaceutical Press; 2002.
  2. Bensky D, Gamble A. Chinese Herbal Medicine: Materia Medica. Revised Ed. Seattle: Eastland Press; 1993.
  3. Foster S, et al. Tyler’s Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies. New York: Haworth Herbal Press; 1999.
  4. Gruenwald J, et al. PDR for Herbal medicines, 2nd ed. Montvale (NJ): Medical Economics Company; 1998.
  5. Huang KC. The Pharmacology of Chinese Herbs, 2nd ed. New York: CRC Press; 1999.
  6. FDA Acts to Seize Ephedra-Containing Dietary Supplements. December 6, 2005. Accessed April 27, 2009.
  7. Boozer C, et al. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord 2001;25:316-24.
  8. Samenuk D, et al. Adverse cardiovascular events temporally associated with ma huang, an herbal source of ephedrine. Mayo Clin Proc 2002;77:12-6.
  9. Haller C, et al. Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use. Clin Pharmacol Ther 2002;71:421-32.
  10. Haller C, Benowitz N. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-8.
  11. Jellin J, editor. Natural Medicines Comprehensive Database. Therapeutic Reseach Faculty; 2002.
  12. News Release. FDA Announces Plans to Prohibit Sales of Dietary Supplements Containing Ephedra. United States Department of Health and Human Services. December 30, 2003. Accessed December 10, 2009.
  13. Food and Drug Administration, HHS. Final rule declaring dietary supplements containing ephedrine alkaloids adulterated because they present an unreasonable risk. Final rule. Fed Regist. 2004 Feb 11;69(28):6787-854.
  14. Naik SD, Freudenberger RS. Ephedra-associated cardiomyopathy. Ann Pharmacother. 2004 Mar;38(3):400-3. Epub 2004 Jan 23.
  15. McBride BF, Karapanos AK, Krudysz A, Kluger J, Coleman CI, White CM. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. JAMA. 2004 Jan 14;291(2):216-21.
  16. Flanagan CM, Kaesberg JL, Mitchell ES, Ferguson MA, Haigney MC. Coronary artery aneurysm and thrombosis following chronic ephedra use. Int J Cardiol. 2010 Feb 18;139(1):e11-3.
  17. Lillegard JB, Porterfield Jr JR. Ephedra-Induced Gastric Mucosal Injury. Case Rep Gastroenterol. 2010 Feb 27;4(1):79-83.
  18. Tang J, Zhou X, Ji H, Zhu D, Wu L. Effects of Ephedra Water Decoction and Cough Tablets containing Ephedra and Liquorice on CYP1A2 and the Pharmacokinetics of Theophylline in Rats. Phytother Res. 2011 Jul 27. doi: 10.1002/ptr.3565. [Epub ahead of print]
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How It Works

Bottom Line: Ephedra is a stimulant that has caused several deaths from heart attack and stroke.

Ephedra contains ephedrine and pseudoephedrine, which are known to stimulate the central nervous system (brain and spinal cord). They activate the “fight or flight” response, resulting in constriction of blood vessels, relaxation and dilation of air passages, appetite suppression, and general stimulant effects. While these effects explain the use of ephedra as a decongestant, weight loss supplement, and anti-asthma agent, in high doses ephedra can raise blood pressure and cause adverse reactions such as stroke and heart attack. Even a single dose of an ephedra containing supplement can cause dangerous increases in blood pressure and effects on heart function. Laboratory studies indicate that ephedra also can kill bacteria on contact, reduce inflammation, and cause contraction of the muscles of the uterus. These effects have not been studied in humans.

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Purported Uses
  • To treat asthma
    Ephedra may stimulate bronchial dilation. Alkaloids from ephedra have been used in over-the-counter medication as asthma remedies and nasal decongestants.
  • To treat coughs and bronchitis
    Ephedra may stimulate bronchial dilation, but there is no proof from clinical trials to support this use. The risk of dangerous side effects of ephedra may outweigh any benefits.
  • To treat the common cold
    No scientific evidence supports this use.
  • To treat infections
    Laboratory studies show that ephedra has antibacterial properties, but there is no proof from clinical trials that ephedra can treat infections.
  • To promote urination
    No scientific evidence supports this use.
  • For strength and stamina
    Ephedra stimulates the central nervous system, but there is no proof from clinical trials to support this use. The risk of dangerous side effects of ephedra may outweigh any benefits.
  • To lose weight
    Even though a few clinical trials suggest that people taking ephedra lose weight, ephedra is not safe to use, even at normal doses.
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Research Evidence

Weight loss:
The effect of a supplement containing ephedra and caffeine on weight loss was examined in a randomized controlled trial with 67 overweight subjects. They were given either the active supplement (containing 72 mg of ephedra and 240 mg of caffeine) or a placebo pill every day for eight weeks. At the end of the study, subjects taking the active supplement lost an average of 8.8 lb as compared to 0.88 lb in the placebo group. Blood triglyceride levels and hip circumference were also reduced in the active treatment group. Several adverse symptoms such as dry mouth, insomnia and headache were reported. It is unclear from this study if the effects were more from ephedra or guarana, or what the long-term health effects are.

Toxicities associated with ephedra:
A group of researchers conducted a review of the F.D.A. Adverse Reaction Monitoring System database to compile a list of toxicities associated with ephedra. They found 926 cases of possible ephedra toxicity between 1995 and 1997. Closer analysis of 37 cases indicated that ephedra and related products can cause stroke, heart attack, and sudden death. These adverse effects are not related to the dose taken and can happen to patients with no prior history of heart disease.

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Patient Warnings
  • The FDA has banned the sales of ephedra-containing dietary supplements. Consumers are urged not to buy or use these products. These products have made unsubstantiated claims and may pose significant health risks. Possible adverse effects include high blood pressure, palpitations, heart attack, stroke, seizures, psychosis and death.
  • Consumption of ephedra may interfere with urine amphetamine test resulting in false-positive results.
  • Ephedra may increase blood glucose levels.
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Do Not Take If
  • You have any of the following conditions: Anxiety, high blood pressure, heart disease, glaucoma, prostate enlargement, or hyperthyroidism.
  • You are pregnant. (Ephedra can stimulate contraction of the uterus).
  • You are taking aspirin (Ephedra may increase the risk of brain hemorrhage (stroke)).
  • You are taking benzodiazepines or other sedatives (Ephedra may lessen their effects).
  • You are taking beta-adrenergic agonists (Ephedra may have additive effects, possibly leading to toxicity).
  • You are taking CNS stimulants (Ephedra may increase the stimulatory effects).
  • You are taking monoamine-oxidase inhibitors (MAO-Is) (Use of ephedra at the same time can cause hypertensive crisis, or dangerously high blood pressure).
  • You are taking theophylline (Ephedra may decrease its effects).
  • You are taking digoxin (Use of ephedra at the same time can cause cardiac arrhythmia).
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Side Effects
  • Headache
  • Hypertension
  • Gastric mucosal injury
  • Palpitations
  • Heart attack
  • Stroke
  • Seizures
  • Insomnia
  • Psychosis
  • Death
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Dosage (Inside MSKCC Only)
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Aliases
Ma Huang
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Last updated: August 18, 2011