Although traditional use of ephedra for respiratory problems does not appear to be unsafe, its use in weight loss, bodybuilding, or energizing products (or as a recreational drug) is dangerous and has resulted in strokes, myocardial infarction, and death.

[LFODPKM ] Letter Key

Latin Name

Ephedra sinica Stapf, E. equisetina Bunge, E. gerardiana Wall ex Stapf, E. intermedia Schenk & C.A. Mey, E. distachya L.

Family

Ephedraceae

Other Common Names

Chinese ephedra, ma huang, cao ma huang, horsetail

Description

• A perennial evergreen, small shrub (20 to 90 cm high) with short, slender green branches and tiny, scale-like leaves; the plant appears leafless.

Part Used

Dried stem, aerial parts

Known Active Constituents

• The active alkaloids are ephedrine, pseudoephedrine, norephedrine, and norpseudoephedrine; ephedra also contains small amounts of (—)N-methyl ephedrine and (+)N-methyl pseudoephedrine. Amounts vary by species but may range from 0.5% to 2.0% alkaloids; the combination of (—)ephedrine and (+)pseudoephedrine account for approximately 90% of total alkaloids. E. intermedia is unusual in that it has a higher proportion of pseudoephedrine than ephedrine.

Mechanism/Pharmacokinetics

• Ephedrine is an orally active sympathomimetic amine with a longer duration of action than epinephrine. Pseudoephedrine is weaker than ephedrine but has similar actions. Both ephedrine and pseudoephedrine stimulate alpha₁, beta₁, and beta₂ adrenoceptors (1).
• Systemic effects of ephedrine include bronchodilation, increased peripheral resistance, increased heart rate, increased blood pressure, urinary retention, increased respiratory rate, increased body temperature, and pupillary dilation (2). C _max occurs approximately 2 hours after ingestion, although one study found a C _max of 3.9 hours (3).
• In a randomized crossover pharmacokinetics study, three commercial ma huang products were compared with a 25 mg ephedrine capsule in 10 participants. Pharmacokinetic parameters were similar for synthetic and botanical ephedrine (4).

[Outline]

• LLatin Name
• FFamily
• OOther Common Names
• DDescription
• PPart Used
• KKnown Active Constituents
• MMechanism/Pharmacokinetics

[CAO ] Letter Key

Clinical Trials

• Weight loss
  • Nine placebo-controlled trials of ephedrine/caffeine (usually 20 mg ephedrine/200 mg caffeine t.i.d.) for weight loss, with a total of about 400 subjects, are split between positive (5–9) and negative (10–13) trials. One treatment-controlled 15-week trial in 103 subjects (81 completed) found ephedra 20 mg/caffeine 200 mg equivalent to 15 mg dexfenfluramine b.i.d. (14). In clinical trials, adverse events, including hypertension, palpitations, insomnia, and headache, were more common in ephedra-treated subjects.
• Ergogenics
  • Two double-blind, placebo-controlled trials by the same investigator found a benefit of ephedrine/caffeine on, respectively, high-intensity aerobic performance in 12 untrained males (15) and on run times in nine recreational runners (16); however, in the more recent trial, 25% experienced nausea and vomiting after exercise.
• Sexual arousal in women
  • In a double-blind, placebo-controlled crossover trial in 20 sexually functional women, ephedrine sulfate (50 mg) significantly facilitated the initial stages of physiologic sexual arousal, measured by vaginal pulse amplitude responses to erotic films; however, it had no significant effect on subjective ratings of sexual arousal (17). Physiologic sexual responses were not increased during presentation of a nonerotic travel film. Significant increases in heart rate were seen approximately 42 minutes after ingestion.
• Heart rate and blood pressure
  • Twelve normotensive adults (including six women) age 23 to 40 were given four capsules of a ma huang product (375 mg each). Heart rate and blood pressure were measured at baseline and 8 hours and 17 hours after ingestion. Half the participants experienced a statistically significant increase in 12-hour heart rate (from approximately 72 beats per minute to 81 beats per minute) (3). Between hours 8 and 11, four participants had statistically significant increases in systolic blood pressure, whereas two had a significant decrease in diastolic blood pressure.

Animal/In Vitro

• An extracted fraction of ephedra inhibits complement in vitro, causing a dose-dependent loss of C2 hemolytic activity (18).

Other Claimed Benefits/Actions

• Weight loss
• Stimulant
• Nasal congestion
• Allergic rhinitis
• Colds
• Sinusitis
• Asthma
• Urticaria
• Enuresis
• Narcolepsy

[Outline]

• CClinical Trials
  • Weight loss
  • Ergogenics
  • Sexual arousal in women
  • Heart rate and blood pressure
• AAnimal/In Vitro
• OOther Claimed Benefits/Actions

[AD ] Letter Key

Adverse Reactions

• Hundreds of adverse events have been associated with ephedra, including reports of stroke, myocardial infarction, chest pain, seizures, insomnia, nausea and vomiting, fatigue, and dizziness (19). A review of 140 adverse events associated with ephedra-containing products reported to the Food and Drug Administration (FDA) between June 1997 and March 1999 found that 31% of cases were considered definitely or probably related and 31% possibly related (20). Among these three categories, 10 deaths and 13 cases of permanent disability resulted. Also in the definitely, probably, or possibly related categories, 47% of adverse events involved cardiovascular symptoms (most commonly hypertension, followed by palpitations or tachycardia) and 18% involved the central nervous system (stroke and seizures). Between 1993 and 1997, the FDA received reports of 34 deaths and about 800 medical and psychiatric complications linked to ephedra (2). Many deaths occurred among young healthy adults, many of whom used an over-the-counter (OTC) product called "Herbal Ecstasy."
• Suicide
  • An ephedra-containing product was used to commit suicide (21).
• Stroke
  • As with cocaine, fatalities are often associated with cerebral vascular abnormalities (22).
• Hypersensitivity myocarditis
  • A 39-year-old African-American hypertensive man taking two to six capsules daily of ma huang for 3 months (the patient was also taking vitamins, pravastatin, and furosemide) developed hypersensitivity myocarditis attributed to ephedra (23).
• Nephrolithiasis
  • A 27-year-old man who was taking 4 to 12 tablets daily of an energy supplement called Pro-Lift (ProPerformance, Pittsburgh, Pennsylvania) containing 170-mg ma huang extract per tablet experienced six episodes of renal colic and four hospitalizations in a 7-month period (21). Gas chromatography and mass spectrometry identified the substrate of the stones as combinations of ephedrine, norephedrine, and pseudoephedrine.
  • The Louis C. Herring and Co. kidney stone database revealed over 200 stones with a similar profile; the incidence was approximately 0.064% (21).
• Psychiatric complications
  • Ephedrine-induced psychosis was first described in 1968; psychotic and affective changes may occur (2). As with amphetamine, ephedrine produces paranoia with a clear sensorium. A review of 20 cases of ephedrine-induced psychoses found delusions in all cases, auditory hallucinations in 90%, visual hallucinations in 45%, affective disturbance in 30%, and agitation with insomnia in 55% (24). Delusions and audio or visual hallucinations may occur, as well as mania. Ephedrine psychosis may last days or weeks and resolves without treatment (2).
  • A 45-year-old man with no history of psychiatric illness or substance abuse, not taking any concurrent medications, developed symptoms of mania 1 month after initiating a regimen of ma huang capsules (25).
  • Another 39-year-old man with no history of psychiatric disorder or substance abuse who had been consuming an ephedra compound in both pill and powder concentrate form to lose weight developed typical symptoms of mania that resolved completely on discontinuation of ephedra (26).
• Hepatitis
  • There is one unconvincing case report of hepatitis diagnosed in a 33-year-old woman about 3 weeks after she began to take "a Chinese medicine product containing ma huang" (27). Symptoms began several days after ingestion. There are no other reports of hepatotoxicity associated with ephedra. No other ingredients in the product are revealed nor was any analysis done of the product. Hepatotoxicity is not uncommon with several other herbs nor with drugs that may be mixed with herbs in Chinese patent medicines, so this case cannot be reasonably attributed to ephedra.

Drug Interactions

• Intracerebral hemorrhage
  • The combination of ephedra with phenylpropanolamine or with caffeine increases the risk of all major adverse effects, including stroke, intracranial hemorrhage, seizures, mania, and psychosis. The combination of ephedra and caffeine has substantially higher side effects than the consumption of either alone.
  • A 68-year-old man with chronic obstructive pulmonary disease (COPD) suffered an intracerebral hemorrhage and necrotizing angiitis of the small vessels attributed to the use of an OTC combination product antiasthma pill that contained theophylline 0.025 g, ephedrine 0.01 g, caffeine 0.015 g, and theobromine 0.025 g (28). The patient had taken four to six tablets a day for 10 years and had used the medication 2 hours before the onset of the stroke. It is unclear to what extent, if any, ephedra contributed to this outcome.

[Outline]

• AAdverse Reactions
  • Suicide
  • Stroke
  • Hypersensitivity myocarditis
  • Nephrolithiasis
  • Psychiatric complications
  • Hepatitis
• DDrug Interactions
  • Intracerebral hemorrhage

[C ] Letter Key

Common Dosage Forms

• The use of ephedra products other than for respiratory conditions, and under the supervision of a knowledgeable health care practitioner, is not recommended. Doses are provided for information only.
• Adult
  • Herb preparations corresponding to 15 to 30 mg total alkaloid/dose, calculated as ephedrine. Maximum daily dosage is 300 mg total alkaloid, calculated as ephedrine, according to Commission E.
• Children
  • Herb preparations corresponding to 0.5 mg total alkaloid per kilogram of body weight per dose. Maximum daily dosage is 2 mg total alkaloid per kg of body weight, according to Commission E.

[Outline]

• CCommon Dosage Forms
  • Adult
  • Children

• Are OTC ephedra products safe?
• Is Mormon tea ephedra?
• Can’t ephedra be used to manufacture speed (methamphetamine)?

Q: Are OTC ephedra products safe?

A: Ephedra is a common and dangerous component of OTC weight loss or bodybuilding supplements. In 1996, sales of drugs containing ephedra totaled $6.5 billion. Amounts of ephedra alkaloids may vary widely; nine commercial supplements had a range of ephedrine-type alkaloids contents of 1.08 to 13.54 mg (4).

Ephedra has been traditionally used (primarily for asthma and other respiratory conditions) in both Western and Eastern herbalism (various forms including toasted with honey are used in traditional Chinese medicine). Adverse effects have not been linked with this traditional use. The use of this herb for weight loss, bodybuilding, energy-boosting, or recreational use has no traditional precedent and is clearly dangerous.

Derivatives of ephedra are also present in OTC drugs. Ephedrine, in doses up to 25 mg/tablet, is common in OTC oral asthma medications. Pseudoephedrine is commonly used as a decongestant and in cough and cold products (1). These products have better warning labels than dietary supplements but can still result in adverse effects.

Q: Is Mormon tea ephedra?

A: Yes, but Mormon tea (Ephedra nevadensis) does not contain ephedrine. There are 40 different species of ephedra, and none of the species that grow in North and Central America contain alkaloids (29).

Q: Can’t ephedra be used to manufacture speed (methamphetamine)?

A: Ephedra can provide starting material for synthesizing methamphetamine and the sale has been regulated in several states because of this. However, ephedra is no longer the primary commercial source for ephedrine because it is much easier to synthesize ephedrine than it is to extract ephedrine from ephedra (29). In addition, ephedrine drug products (including OTC bronchodilators for asthma) can also be used to manufacture speed (19).

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